Change search
Refine search result
1234567 1 - 50 of 316
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    A. Strumpfer, Johan
    et al.
    University of Illinois at Urbana Champaign, Urbana, IL, USA; Beckman Institute, Urbana, IL, USA.
    von Castelmur, Eleonore
    Institute of Integrative Biology, University of Liverpool, Liverpool, IL, USA.
    Franke, Barbara
    Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
    Barbieri, Sonia
    Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
    Bogomolovas, Julijus
    Universitätsmedizin Mannheim, Mannheim, Germany.
    Qadota, Hiroshi
    Department of Pathology, Emory University, Atlanta, GA, USA.
    Konarv, Petr
    European Molecular Biology Laboratory, Hamburg, Germany.
    Svergun, Dmitri
    European Molecular Biology Laboratory, Hamburg, Germany.
    Labeit, Siegfried
    Department for Integrative Pathophysiology, Universitätsmedizin Mannheim, Mannheim, Germany.
    Schulten, Klaus
    University of Illinois at Urbana Champaign, Urbana, IL, USA Beckman Institute, Urbana, IL, USA.
    Benian, Guy
    Department of Pathology, Emory University, Atlanta, GA, USA.
    Mayans, Olga
    Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
    Stretching of Twitchin Kinase2012In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 102, no 3 Supplement 1, p. 361a-362aArticle in journal (Refereed)
    Abstract [en]

    The giant proteins from the titin family, that form cytoskeletal filaments, have emerged as key mechanotransducers in the sarcomere. These proteins contain a conserved kinase region, which is auto-inhibited by a C-terminal tail domain. The inhibitory tail domain occludes the active sites of the kinases, thus preventing ATP from binding. It was proposed that through application of a force, such as that arising during muscle contraction, the inhibitory tail becomes detached, lifting inhibition. The force-sensing ability of titin kinase was demonstrated in AFM experiments and simulations [Puchner, et al., 2008, PNAS:105, 13385], which showed indeed that mechanical forces can remove the autoinhibitory tail of titin kinase. We report here steered molecular dynamics simulations (SMD) of the very recently resolved crystal structure of twitchin kinase, containing the kinase region and flanking fibronectin and immuniglobulin domains, that show a variant mechanism. Despite the significant structural and sequence similarity to titin kinase, the autoinhibitory tail of twitchin kinase remains in place upon stretching, while the N-terminal lobe of the kinase unfolds. The SMD simulations also show that the detachment and stretching of the linker between fibronectin and kinase regions, and the partial extension of the autoinhibitory tail, are the primary force-response. We postulate that this stretched state, where all structural elements are still intact, may represent the physiologically active state.

  • 2.
    Adler, Jeremy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quantification of Colocalisation; Co-Occurrence, Correlation, Empty Voxels, Regions of Interest and Thresholding2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 602A-602AArticle in journal (Other academic)
    Abstract [en]

    Measuring colocalisation is not straightforward with a plethora of coefficients that encapsulate different definitions. Measurements may also be implemented differently. Not only do measurements differ; interconversion is impossible making comparisons challenging. There is a need to cull coefficients and for clear definitions of what precisely is meant by colocalisation in individual studies. Colocalisation can be considered to have two components; co-occurrence which reports whether the fluorophores are found together and correlation which reports on the similarity in their patterns of intensity.

  • 3.
    Ahlinder, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Ekstrand-Hammarstrom, Barbro
    Geladi, Paul
    Österlund, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Large Uptake of Titania and Iron Oxide Nanoparticles in the Nucleus of Lung Epithelial Cells as Measured by Raman Imaging and Multivariate Classification2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 105, no 2, p. 310-319Article in journal (Refereed)
    Abstract [en]

    It is a challenging task to characterize the biodistribution of nanoparticles in cells and tissue on a subcellular level. Conventional methods to study the interaction of nanoparticles with living cells rely on labeling techniques that either selectively stain the particles or selectively tag them with tracer molecules. In this work, Raman imaging, a label-free technique that requires no extensive sample preparation, was combined with multivariate classification to quantify the spatial distribution of oxide nanoparticles inside living lung epithelial cells (A549). Cells were exposed to TiO2 (titania) and/or alpha-FeO(OH) (goethite) nanoparticles at various incubation times (4 or 48 h). Using multivariate classification of hyperspectral Raman data with partial least-squares discriminant analysis, we show that a surprisingly large fraction of spectra, classified as belonging to the cell nucleus, show Raman bands associated with nanoparticles. Up to 40% of spectra from the cell nucleus show Raman bands associated with nanoparticles. Complementary transmission electron microscopy data for thin cell sections qualitatively support the conclusions.

  • 4.
    Akanda, Nesar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Biophysical properties of the apoptosis-inducing plasma membrane voltage-dependent anion channel2006In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 90, no 12, p. 4405-4417Article in journal (Refereed)
    Abstract [en]

    Ion channels in the plasma membrane play critical roles in apoptosis. In a recent study we found that a voltage-dependent anion channel in the plasma membrane (VDACpl) of neuronal hippocampal cell line (HT22) cells was activated during apoptosis and that channel block prevented apoptosis. Whether or not VDACpl is identical to the mitochondrial VDACmt has been debated. Here, we biophysically characterize the apoptosis-inducing VDACpl and compare it with other reports of VDACpls and VDACmt. Excised membrane patches of apoptotic HT22 cells were studied with the patch-clamp technique. VDACpl has a large main-conductance state (400 pS) and occasionally subconductance states of µ28 pS and 220 pS. The small subconductance state is associated with long-lived inactivated states, and the large subconductance state is associated with excision of the membrane patch and subsequent activation of the channel. The open-probability curve is bell shaped with its peak around 0mV and is blocked by 30µM Gd3+. The gating can be described by a symmetrical seven-state model with one open state and six closed or inactivated states. These channel properties are similar to those of VDACmt and other VDACpls and are discussed in relation to apoptosis.

  • 5.
    Alam, Md Khorshed
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vinklarek, Ivo
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Lennart B-Å
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sachl, Radek
    Fluorescence Studies of Lipid Distribution in Bilayers under Oxidative Stress2019In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 116, no 3, p. 508A-508AArticle in journal (Other academic)
  • 6. Alam, MT
    et al.
    Yamada, T
    Carlsson, Uno
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Ikai, A
    The importance of being knotted: Effects of the C-terminal knot structure on enzymatic and mechanical properties of bovine carbonic anhydrase II2003In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 84, no 2, p. 159A-159AConference paper (Other academic)
  • 7. Alizadehheidari, Mohammadreza
    et al.
    Werner, Erik
    Noble, Charleston
    Nyberg, Lena
    Fritzsche, Joachim
    Mehlig, Bernhard
    Tegenfeldt, Jonas
    Ambjoernsson, Tobias
    Persson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Westerlund, Fredrik
    Nanoconfined Circular DNA2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 274A-274AArticle in journal (Other academic)
    Abstract [en]

    Nanofluidic channels have become a versatile tool to manipulate single DNA molecules. They allow investigation of confined single DNA molecules from a fundamental polymer physics perspective as well as for example in DNA barcoding techniques.

  • 8.
    Alizadehheidari, Mohammadreza
    et al.
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Werner, Erik
    Gothenburg Univ, Phys, Gothenburg, Sweden..
    Noble, Charleston
    Lund Univ, Phys, Lund, Sweden..
    Nyberg, Lena
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Fritzsche, Joachim
    Chalmers, Appl Phys, S-41296 Gothenburg, Sweden..
    Persson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Mehlig, Bernhard
    Gothenburg Univ, Phys, Gothenburg, Sweden..
    Tegenfeldt, Jonas
    Lund Univ, Solid State Phys, Gothenburg, Sweden..
    Ambjornsson, Tobias
    Lund Univ, Phys, Lund, Sweden..
    Westerlund, Fredrik
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Unfolding of Nanoconfined Circular DNA2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2, p. 231A-231AArticle in journal (Other academic)
  • 9.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Andersson, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Chalmers, Dept Chem & Chem Engn, S-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Chem Engn, S-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 110, no 6, p. 1255-1263Article in journal (Refereed)
    Abstract [en]

    DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.

  • 10.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Andersson, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA..
    Westerlund, Fredrik
    Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Resolving the DNA Binding Mode of a Rotationally Flexible Binuclear Ruthenium Complex2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2, p. 396A-396AArticle in journal (Other academic)
  • 11.
    Almqvist, Nils
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Material Science.
    Bhatia, R
    Neuroscience Research Institute, University of California, Santa Barbara.
    Primbs, G
    Neuroscience Research Institute, University of California, Santa Barbara.
    Desai, N
    NutraSweet Company, Chicago.
    Banerjee, S
    Department of Chemical Engineering, University of California, Santa Barbara.
    Lal, R
    Neuroscience Research Institute, University of California, Santa Barbara.
    Elasticity and adhesion force mapping reveals real-time clustering of growth factor receptors and associated changes in local cellular rheological properties2004In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 86, no 3, p. 1753-1762Article in journal (Refereed)
    Abstract [en]

    Cell surface macromolecules such as receptors and ion channels serve as the interface link between the cytoplasm and the extracellular region. Their density, distribution, and clustering are key spatial features influencing effective and proper physical and biochemical cellular responses to many regulatory signals. In this study, the effect of plasma-membrane receptor clustering on local cell mechanics was obtained from maps of interaction forces between antibody-conjugated atomic force microscope tips and a specific receptor, a vascular endothelial growth factor (VEGF) receptor. The technique allows simultaneous measurement of the real-time motion of specific macromolecules and their effect on local rheological properties like elasticity. The clustering was stimulated by online additions of VEGF, or antibody against VEGF receptors. VEGF receptors are found to concentrate toward the cell boundaries and cluster rapidly after the online additions commence. Elasticity of regions under the clusters is found to change remarkably, with order-of-magnitude stiffness reductions and fluidity increases. The local stiffness reductions are nearly proportional to. receptor density and, being concentrated near the cell edges, provide a mechanism for cell growth and angiogenesis.

  • 12. Aman, K.
    et al.
    Lindahl, E.
    Edholm, Olle
    KTH, Superseded Departments, Physics.
    Hakansson, P.
    Westlund, P. O.
    Structure and dynamics of interfacial water in an L-alpha phase lipid bilayer from molecular dynamics simulations2003In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 84, no 1, p. 102-115Article in journal (Refereed)
    Abstract [en]

    Based on molecular dynamics simulations, an analysis of structure and dynamics is performed on interfacial water at a liquid crystalline dipalmitoylphosphatidycholine/water system. Water properties relevant for understanding NMR relaxation are emphasized. The first and second rank orientational order parameters of the water O-H bonds were calculated, where the second rank order parameter is in agreement with experimental determined quadrupolar splittings. Also, two different interfacial water regions (bound water regions) are revealed with respect to different signs of the second rank order parameter. The water reorientation correlation function reveals a mixture of fast and slow decaying parts. The fast (ps) part of the correlation function is due to local anisotropic water reorientation whereas the much slower part is due to more complicated processes including lateral diffusion along the interface and chemical exchange between free and bound water molecules. The 100-ns-long molecular dynamics simulation at constant pressure (1 atm) and at a temperature of 50degreesC of 64 lipid molecules and 64 x 23 water molecules lack a slow water reorientation correlation component in the ns time scale. The (H2O)-H-2 powder spectrum of the dipalmitoylphosphatidycholine/water system is narrow and consequently, the NMR relaxation time T-2 is too short compared to experimental results.

  • 13.
    Aman, Ken
    et al.
    Umeå University.
    Lindahl, Erik
    KTH, Superseded Departments, Physics.
    Edholm, Olle
    KTH, Superseded Departments, Physics.
    Håkansson, Pär
    Umeå University.
    Westlund, Per-Olof
    Umeå University.
    Structure and dynamics of interfacial water in an Lalpha phase lipid bilayer from molecular dynamics simulations.2003In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 84, no 1, p. 102-15Article in journal (Refereed)
    Abstract [en]

    Based on molecular dynamics simulations, an analysis of structure and dynamics is performed on interfacial water at a liquid crystalline dipalmitoylphosphatidycholine/water system. Water properties relevant for understanding NMR relaxation are emphasized. The first and second rank orientational order parameters of the water O-H bonds were calculated, where the second rank order parameter is in agreement with experimental determined quadrupolar splittings. Also, two different interfacial water regions (bound water regions) are revealed with respect to different signs of the second rank order parameter. The water reorientation correlation function reveals a mixture of fast and slow decaying parts. The fast (ps) part of the correlation function is due to local anisotropic water reorientation whereas the much slower part is due to more complicated processes including lateral diffusion along the interface and chemical exchange between free and bound water molecules. The 100-ns-long molecular dynamics simulation at constant pressure (1 atm) and at a temperature of 50 degrees C of 64 lipid molecules and 64 x 23 water molecules lack a slow water reorientation correlation component in the ns time scale. The (2)H(2)O powder spectrum of the dipalmitoylphosphatidycholine/water system is narrow and consequently, the NMR relaxation time T(2) is too short compared to experimental results.

  • 14.
    Amselem, Elias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Marklund, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Kipper, Kalle
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Johansson, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Deindl, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Real- Time Single Protein Tracking with Polarization Readout using a Confocal Microscope2017In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 112, no 3, p. 295A-295AArticle in journal (Other academic)
  • 15.
    Andersson, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Physics.
    Fällman, Erik
    Umeå University, Faculty of Science and Technology, Physics.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Axner, Ove
    Umeå University, Faculty of Science and Technology, Physics.
    A sticky chain model of the elongation and unfolding of escherichia coli P pili under stress2006In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 90, no 5, p. 1521-1534Article in journal (Refereed)
    Abstract [en]

    A model of the elongation of P pili expressed by uropathogenic Escherichia coli exposed to stress is presented. The model is based upon the sticky chain concept, which is based upon Hooke’s law for elongation of the layer-to-layer and head-to-tail bonds between neighboring units in the PapA rod and a kinetic description of the opening and closing of bonds, described by rate equations and an energy landscape model. It provides an accurate description of the elongation behavior of P pili under stress and supports a hypothesis that the PapA rod shows all three basic stereotypes of elongation/unfolding: elongation of bonds in parallel, the zipper mode of unfolding, and elongation and unfolding of bonds in series. The two first elongation regions are dominated by a cooperative bond opening, in which each bond is influenced by its neighbor, whereas the third region can be described by individual bond opening, in which the bonds open and close randomly. A methodology for a swift extraction of model parameters from force-versus-elongation measurements performed under equilibrium conditions is derived. Entities such as the free energy, the stiffness, the elastic elongation, the opening length of the various bonds, and the number of PapA units in the rod are determined.

  • 16.
    Andersson, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Physics.
    Fällman, Erik
    Umeå University, Faculty of Science and Technology, Physics.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Axner, Ove
    Umeå University, Faculty of Science and Technology, Physics.
    Dynamic Force Spectroscopy of E. coli P Pili2006In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 91, no 7, p. 2717-2725Article in journal (Refereed)
    Abstract [en]

    Surface organelles (so-called pili) expressed on the bacterial membrane mediate the adhesion of Escherichia coli causing urinary tract infection. These pili possess some extraordinary elongation properties that are assumed to allow a close bacterium-to-host contact even in the presence of shear forces caused by urine flow. The elongation properties of P pili have therefore been assessed for low elongation speeds (steady-state conditions). This work reports on the behavior of P pili probed by dynamic force spectroscopy. A kinetic model for the unfolding of a helixlike chain structure is derived and verified. It is shown that the unfolding of the quaternary structure of the PapA rod takes place at a constant force that is almost independent of elongation speed for slow elongations (up to ~0.4 μm/s), whereas it shows a dynamic response with a logarithmic dependence for fast elongations. The results provide information about the energy landscape and reaction rates. The bond length and thermal bond opening and closure rates for the layer-to-layer bond have been assessed to ~0.76 nm, ~0.8 Hz, and ~8 GHz, respectively. The results also support a previously constructed sticky-chain model for elongation of the PapA rod that until now had been experimentally verified only under steady-state conditions.

  • 17.
    Andersson, Magnus
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics.
    Lindahl, Erik
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    White, Stephen H.
    Univ Calif Irvine, Irvine, CA USA..
    Kaback, Ronald H.
    Univ Calif Los Angeles, Los Angeles, CA USA..
    The Molecular Basis for Substrate Specificity in Lactose Permease2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2, p. 309A-309AArticle in journal (Other academic)
  • 18.
    Andersson, Magnus
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mattle, Daniel
    Sitsel, Oleg
    Nielsen, Anna Marie
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    White, Stephen H.
    Nissen, Poul
    Gourdon, Pontus
    Transport Pathway in Cu+ P-Type ATPases2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 427A-427AArticle in journal (Other academic)
  • 19.
    Andersson, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Physics.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Fällman, Erik
    Umeå University, Faculty of Science and Technology, Physics.
    The biomechanical properties of E. coli pili for urinary tract attachment reflect the host environment2007In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 93, no 9, p. 3008-3014Article in journal (Refereed)
    Abstract [en]

    Uropathogenic Escherichia coli express pili that mediate binding to host tissue cells. We demonstrate with in situ force measuring optical tweezers that the ability of P and type 1 pili to elongate by unfolding under exposure to stress is a shared property with some differences. The unfolding force of the quaternary structures under equilibrium conditions is similar, 28 ± 2 and 30 ± 2 pN for P pili and type 1 pili, respectively. However, type 1 pili are found to be more rigid than P pili through their stronger layer-to-layer bonds. It was found that type 1 pili enter a dynamic regime at elongation speeds of 6 nm/s, compared to 400 nm/s for P pili; i.e., it responds faster to an external force. This possibly helps type 1 to withstand the irregular urine flow in the urethra as compared to the more constant urine flow in the upper urinary tract. Also, it was found that type 1 pili refold during retraction at two different levels that possibly could be related to several possible configurations. Our findings highlight functions that are believed to be of importance for the bacterial ability to sustain a basic antimicrobial mechanism of the host and for bacterial colonization.

  • 20.
    Andér, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Luzhkov, Victor B.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Åqvist, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Ligand binding to the voltage-gated Kv1.5 potassium channel in the open state - Docking and computer simulations of a homology model2008In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 94, no 3, p. 820-831Article in journal (Refereed)
    Abstract [en]

    The binding of blockers to the human voltage-gated Kv1.5 potassium ion channel is investigated using a three-step procedure consisting of homology modeling, automated docking, and binding free energy calculations from molecular dynamics simulations, in combination with the linear interaction energy method. A reliable homology model of Kv1.5 is constructed using the recently published crystal structure of the Kv1.2 channel as a template. This model is expected to be significantly more accurate than earlier ones based on less similar templates. Using the three-dimensional homology model, a series of blockers with known affinities are docked into the cavity of the ion channel and their free energies of binding are calculated. The predicted binding free energies are in very good agreement with experimental data and the binding is predicted to be mainly achieved through nonpolar interactions, whereas the relatively small differences in the polar contribution determine the specificity. Apart from confirming the importance of residues V505, I508, V512, and V516 for ligand binding in the cavity, the results also show that A509 and P513 contribute significantly to the nonpolar binding interactions. Furthermore, we find that pharmacophore models based only on optimized free ligand conformations may not necessarily capture the geometric features of ligands bound to the channel cavity. The calculations herein give a detailed structural and energetic picture of blocker binding to Kv1.5 and this model should thus be useful for further ligand design efforts.

  • 21.
    Antzutkin, Oleg
    et al.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Balbach, John J.
    National Institutes of Health.
    Tycko, Robert
    National Institutes of Health.
    Site-Specific Identification of Non-ß-Strand Conformations in Alzheimer's ß-Amyloid Fibrils by Solid-State NMR2003In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 84, no 5, p. 3326-3335Article in journal (Refereed)
    Abstract [en]

    The most well-established structural feature of amyloid fibrils is the cross-ß motif, an extended ß-sheet structure formed by ß-strands oriented perpendicular to the long fibril axis. Direct experimental identification of non-ß-strand conformations in amyloid fibrils has not been reported previously. Here we report the results of solid-state NMR measurements on amyloid fibrils formed by the 40-residue ß-amyloid peptide associated with Alzheimer's disease (Aß1-40), prepared synthetically with pairs of 13C labels at consecutive backbone carbonyl sites. The measurements probe the peptide backbone conformation in residues 24-30, a segment where a non-ß-strand conformation has been suggested by earlier sequence analysis, cross-linking experiments, and molecular modeling. Data obtained with the fpRFDR-CT, DQCSA, and 2D MAS exchange solid-state NMR techniques, which provide independent constraints on the and backbone torsion angles between the labeled carbonyl sites, indicate non-ß-strand conformations at G25, S26, and G29. These results represent the first site-specific identification and characterization of non-ß-strand peptide conformations in an amyloid fibril

  • 22.
    Ashrafzadeh, Parham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dinic, Jelena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Actin Filaments Attachment to the Plasma Membrane Cause the Formation of Ordered Lipid Domains in Live Cells2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 706A-706AArticle in journal (Other academic)
    Abstract [en]

    The aim of this study was to investigate the relationship between ordered plasma membrane nanodomains and actin filaments using di-4-ANEPPDHQ and laurdan together with the reagents that affect actin filament dynamics in live Jurkat and primary T cells. The degree of lipid packing can be quantified using polarity sensitive membrane dyes such as laurdan and di-4-ANEPPDHQ. These two dyes display a red shift in their emission peaks for membranes in ld phase relative to lo phase. Laurdan is uncharged and can easily flip between two leaflets of the plasma membrane and we demonstrate that it reports equally on the two leaflets of the plasma membrane.

  • 23.
    Badell, Maria Valldeperas
    et al.
    Lund Univ, Phys Chem, Lund, Sweden.;Lund Univ, NanoLund, Lund, Sweden..
    Dabkowska, Aleksandra
    Lund Univ, Phys Chem, Lund, Sweden.;Lund Univ, NanoLund, Lund, Sweden..
    Naidjonoka, Polina
    Lund Univ, Phys Chem, Lund, Sweden..
    Welbourn, Rebecca
    Rutherford Appleton Lab, STFC, ISIS Neutron & Muon Source, Didcot, Oxon, England..
    Pålsson, Gunnar K.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics. Inst Laue Langevin, Grenoble, France..
    Barauskas, Justas
    Camurus AB, Lund, Sweden.;Malmo Univ, Biomed Sci, Malmo, Sweden..
    Nylander, Tommy
    Lund Univ, Phys Chem, Lund, Sweden.;Lund Univ, NanoLund, Lund, Sweden..
    Lipid Sponge-Phase Nanoparticles as Carriers for Enzymes2018In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 3, p. 15A-15AArticle in journal (Other academic)
  • 24.
    Balbach, John J.
    et al.
    National Institutes of Health.
    Petkova, Aneta T.
    National Institutes of Health.
    Oyler, Nathan A.
    National Institutes of Health.
    Antzutkin, Oleg
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Gordon, David J.
    University of Chicago.
    Supramolecular structure in full-length Alzheimer's -amyloid fibrils: evidence for a parallel -sheet organization from solid-state nuclear magnetic resonance2002In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 83, no 2, p. 1205-1216Article in journal (Refereed)
  • 25.
    Barg, Sebastian
    et al.
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Ma, Xiaosong
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Eliasson, Lena
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Galvanovskis, Juris
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Göpel, Sven O
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Obermüller, Stefanie
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Platzer, Josef
    Institut für Biochemische Pharmakologie, Innsbruck.
    Renström, Erik
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Trus, Michel
    Department of Biological Chemistry, The Hebrew University of Jerusalem.
    Atlas, Daphne
    Department of Biological Chemistry, The Hebrew University of Jerusalem.
    Striessnig, Jörg
    Institut für Biochemische Pharmakologie, Innsbruck.
    Rorsman, Patrik
    Department of Molecular and Cellular Physiology, Institute of Physiological Sciences, Lund University, Lund.
    Fast exocytosis with few Ca(2+) channels in insulin-secreting mouse pancreatic B cells2001In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 81, no 6, p. 3308-23Article in journal (Refereed)
    Abstract [en]

    The association of L-type Ca(2+) channels to the secretory granules and its functional significance to secretion was investigated in mouse pancreatic B cells. Nonstationary fluctuation analysis showed that the B cell is equipped with <500 alpha1(C) L-type Ca(2+) channels, corresponding to a Ca(2+) channel density of 0.9 channels per microm(2). Analysis of the kinetics of exocytosis during voltage-clamp depolarizations revealed an early component that reached a peak rate of 1.1 pFs(-1) (approximately 650 granules/s) 25 ms after onset of the pulse and is completed within approximately 100 ms. This component represents a subset of approximately 60 granules situated in the immediate vicinity of the L-type Ca(2+) channels, corresponding to approximately 10% of the readily releasable pool of granules. Experiments involving photorelease of caged Ca(2+) revealed that the rate of exocytosis was half-maximal at a cytoplasmic Ca(2+) concentration of 17 microM, and concentrations >25 microM are required to attain the rate of exocytosis observed during voltage-clamp depolarizations. The rapid component of exocytosis was not affected by inclusion of millimolar concentrations of the Ca(2+) buffer EGTA but abolished by addition of exogenous L(C753-893), the 140 amino acids of the cytoplasmic loop connecting the 2(nd) and 3(rd) transmembrane region of the alpha1(C) L-type Ca(2+) channel, which has been proposed to tether the Ca(2+) channels to the secretory granules. In keeping with the idea that secretion is determined by Ca(2+) influx through individual Ca(2+) channels, exocytosis triggered by brief (15 ms) depolarizations was enhanced 2.5-fold by the Ca(2+) channel agonist BayK8644 and 3.5-fold by elevating extracellular Ca(2+) from 2.6 to 10 mM. Recordings of single Ca(2+) channel activity revealed that patches predominantly contained no channels or many active channels. We propose that several Ca(2+) channels associate with a single granule thus forming a functional unit. This arrangement is important in a cell with few Ca(2+) channels as it ensures maximum usage of the Ca(2+) entering the cell while minimizing the influence of stochastic variations of the Ca(2+) channel activity.

  • 26.
    Barrozo, Alexandre H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Harnessing Promiscuity Patterns to Map Evolution in the Alkaline Phosphatase Superfamily2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 104, no 2, p. 232A-232AArticle in journal (Other academic)
  • 27.
    Barrozo, Alexandre H.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Carvalho, Alexandra Pires
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Understanding Functional Evolution in the Alkaline Phosphatase Superfamily2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 675A-675AArticle in journal (Other academic)
    Abstract [en]

    Over the past 40 years, it has been demonstrated that many enzymes are capable of promiscuous catalytic activities, facilitating the turnover of more than one chemically distinct substrate. This has been argued to play an important role in enzyme evolution, with highly promiscuous progenitor enzymes evolving under evolutionary pressure to modern day specialists, while still retaining some level of their former promiscuous activities1. This theory has been extensively tested by different experiments using in vitro evolution2. The alkaline phosphatase superfamily members provide a particularly attractive showcase for studying enzyme promiscuity, as they often show reciprocal promiscuity, in that the native reaction for one member is often a side-reaction for another3. While deceptively similar, their catalyzed reactions (cleavage of P-O and S-O bonds) proceed via distinct transition states and protonation requirements4,5. We present detailed computational studies of the promiscuous catalytic activity of three evolutionarily related members: the arylsulfatase from Pseudomonas aeruginosa6, and the phosphonate monoester hydrolases from Burkholderia caryophili7and Rhizobium leguminosarum8. By tracking their structural and electrostatic features, and comparing to other known members of the superfamily, we provide an atomic-level map for functional evolution within this superfamily.

  • 28. Basanez, G
    et al.
    RuizArguello, MB
    Alonso, A
    Goni, FM
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Morphological changes induced by phospholipase C and by sphingomyelinase on large unilamellar vesicles: a cryo-transmission electron microscopy study of liposome fusion.1997In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 72, no 6, p. 2630-2637Article in journal (Refereed)
    Abstract [en]

    Cryo-transmission electron microscopy has been applied to the study of the changes induced by phospholipase C on large unilamellar vesicles containing phosphatidylcholine, as well as to the action of sphingomyelinase on vesicles containing sphingomyelin. In both cases vesicle aggregation occurs as the earliest detectable phenomenon; later, each system behaves differently. Phospholipase C induces vesicle fusion through an intermediate consisting of aggregated and closely packed vesicles (the ''honeycomb structure'') that finally transforms into large spherical vesicles. The same honeycomb structure is also observed in the absence of enzyme when diacylglycerols are mixed with the other lipids in organic solution, before hydration. In this case the sample then evolves toward a cubic phase. The fact that the same honeycomb intermediate can lead to vesicle fusion (with enzyme-generated diacylglycerol) or to a cubic phase (when diacylglycerol is premixed with the lipids) is taken in support of the hypothesis according to which a highly curved lipid structure (''stalk'') would act as a structural intermediate in membrane fusion, Sphingomyelinase produces complete leakage of vesicle aqueous contents and an increase in size of about one-third of the vesicles. A mechanism of vesicle opening and reassembling is proposed in this case.

  • 29. Beckham, Gregg T.
    et al.
    Bomble, Yannick J.
    Matthews, James F.
    Taylor, Courtney B.
    Resch, Michael G.
    Yarbrough, John M.
    Decker, Steve R.
    Bu, Lintao
    Zhao, Xiongce
    McCabe, Clare
    Wohlert, Jakob
    Bergenstråhle, Malin
    KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Brady, John W.
    Adney, William S.
    Himmel, Michael E.
    Crowley, Michael F.
    The O-Glycosylated Linker from the Trichoderma reesei Family 7 Cellulase Is a Flexible, Disordered Protein2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 99, no 11, p. 3773-3781Article in journal (Refereed)
    Abstract [en]

    Fungi and bacteria secrete glycoprotein cocktails to deconstruct cellulose Cellulose degrading enzymes (cellulases) are often modular with catalytic domains for cellulose hydrolysis and carbohydrate binding modules connected by linkers rich in serine and threonine with O-glycosylation Few studies have probed the role that the linker and O-glycans play in catalysis Since different expression and growth conditions produce different glycosylation patterns that affect enzyme activity the structure function relationships that glycosylation imparts to linkers are relevant for understanding cellulase mechanisms Here the linker of the Trichoderma reesei Family 7 cellobiohydrolase (Cel7A) is examined by simulation Our results suggest that the Cel7A linker is an intrinsically disordered protein with and without glycosylation Contrary to the predominant view the O-glycosylation does not change the stiffness of the linker as measured by the relative fluctuations in the end to end distance rather it provides a 16 A extension thus expanding the operating range of Cel7A We explain observations from previous biochemical experiments in the light of results obtained here and compare the Cel7A linker with linkers from other cellulases with sequence based tools to predict disorder This preliminary screen indicates that linkers from Family 7 enzymes from other genera and other cellulases within T reesei may not be as disordered warranting further study

  • 30.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Actomyosin Interactions and Different Structural States of Actin Filaments2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 104, no 2, p. 480A-481AArticle in journal (Other academic)
  • 31.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Altered Structural State of Actin Filaments Upon MYOSIN II Binding2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2 Supplement 1, p. 299A-300A, article id 1499-PosArticle in journal (Other academic)
  • 32.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Karolinska Institutet ; McGill Univ, Canada.
    Rahman, Mohammad A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Delhi Technol Univ, India.
    Takatsuki, Hideyo
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 7, p. 1465-1477Article in journal (Refereed)
    Abstract [en]

    Actin filaments have key roles in cell motility but are generally claimed to be passive interaction partners in actin-myosin -based motion generation. Here, we present evidence against this static view based on an altered myosin-induced actin filament gliding pattern in an in vitro motility assay at varied [MgATP]. The statistics that characterize the degree of meandering of the actin filament paths suggest that for [MgATP] >= 0.25 mM, the flexural rigidity of heavy meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or slightly lower (with phalloidin) than that of HMM-free filaments observed in solution without surface tethering. When [MgATP] was reduced to <= 0.1 mM, the actin filament paths in the in vitro motility assay became appreciably more winding in both the presence and absence of phalloidin. This effect of lowered [MgATP] was qualitatively different from that seen when HMM was mixed with ATP-insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25-30%). In particular, the addition of NEM-HMM increased a non-Gaussian tail in the path curvature distribution as well as the number of events in which different parts of an actin filament followed different paths. These effects were the opposite of those observed with reduced [MgATP]. Theoretical modeling suggests a 30-40% lowered flexural rigidity of the actin filaments at [MgATP] <= 0.1 mM and local bending of the filament front upon each myosin head attachment. Overall, the results fit with appreciable structural changes in the actin filament during actomyosin-based motion generation, and modulation of the actin filament mechanical properties by the dominating chemomechanical actomyosin state.

  • 33. Benninger, R. K. P.
    et al.
    Önfelt, Björn
    Neil, M. A. A.
    Davis, D. M.
    French, P. M. W.
    Fluorescence imaging of two-photon linear dichroism: Cholesterol depletion disrupts molecular orientation in cell membranes2005In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 88, no 1, p. 609-622Article in journal (Refereed)
    Abstract [en]

    The plasma membrane of cells is an ordered environment, giving rise to anisotropic orientation and restricted motion of molecules and proteins residing in the membrane. At the same time as being an organized matrix of defined structure, the cell membrane is heterogeneous and dynamic. Here we present a method where we use fluorescence imaging of linear dichroism to measure the orientation of molecules relative to the cell membrane. By detecting linear dichroism as well as fluorescence anisotropy, the orientation parameters are separated from dynamic properties such as rotational diffusion and homo energy transfer ( energy migration). The sensitivity of the technique is enhanced by using two-photon excitation for higher photo-selection compared to single photon excitation. We show here that we can accurately image lipid organization in whole cell membranes and in delicate structures such as membrane nanotubes connecting two cells. The speed of our wide-field imaging system makes it possible to image changes in orientation and anisotropy occurring on a subsecond timescale. This is demonstrated by time-lapse studies showing that cholesterol depletion rapidly disrupts the orientation of a fluorophore located within the hydrophobic region of the cell membrane but not of a surface bound probe. This is consistent with cholesterol having an important role in stabilizing and ordering the lipid tails within the plasma membrane.

  • 34. Benninger, Richard K. P.
    et al.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Young, Stephen
    Taner, Sabrina B.
    Culley, Fiona I.
    Schnyder, Tim
    Neil, Mark A. A.
    Wuestner, Daniel
    French, Paul M. W.
    Davis, Daniel M.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Live Cell Linear Dichroism Imaging Reveals Extensive Membrane Ruffling within the Docking Structure of Natural Killer Cell Immune Synapses2009In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 96, no 2, p. L13-L15Article in journal (Refereed)
    Abstract [en]

    We have applied fluorescence imaging of two-photon linear dichroism to measure the subresolution organization of the cell membrane during formation of the activating (cytolytic) natural killer (NK) cell immune synapse (IS). This approach revealed that the NK cell plasma membrane is convoluted into ruffles at the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse imaging showed that the membrane ruffles formed at the initial point of contact between NK cells and target cells and then spread radialy across the intercellular contact as the size of the IS increased, becoming absent from the center of the mature synapse. Understanding the role of such extensive membrane ruff ling in the assembly of cytolytic synapses is an intriguing new goal.

  • 35. Beugin, S
    et al.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Ollivon, M
    Lesieur, S
    New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.1998In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 74, no 6, p. 3198-3210Article in journal (Other academic)
    Abstract [en]

    Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C(16)G(2)) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C(16)G(2)/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks.

  • 36.
    Björnham, Oscar
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Axner, Ove
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Catch-Bond behavior of bacteria binding by slip bonds2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 99, no 5, p. 1331-1341Article in journal (Refereed)
    Abstract [en]

    It is shown that multipili-adhering bacteria expressing helix-like pili binding by slip bonds can show catch-bond behavior. When exposed to an external force, such bacteria can mediate adhesion to their hosts by either of two limiting means: sequential or simultaneous pili force exposure (referring to when the pili mediate force in a sequential or simultaneous manner, respectively). As the force is increased, the pili can transition from sequential to simultaneous pili force exposure. Since the latter mode of adhesion gives rise to a significantly longer bacterial adhesion lifetime than the former, this results in a prolongation of the lifetime, which shows up as a catch-bond behavior. The properties and conditions of this effect were theoretically investigated and assessed in some detail for dual-pili-adhering bacteria, by both analytical means and simulations. The results indicate that the adhesion lifetime of such bacteria can be prolonged by more than an order of magnitude. This implies that the adhesion properties of multibinding systems cannot be directly conveyed to the individual adhesion-receptor bonds.

  • 37. Blau, Christian
    Gromaps: A Gromacs-Based Toolset to Analyse Density Maps Derived from Molecular Dynamics Simulations2019In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 116, no 1, p. 4-11Article in journal (Refereed)
    Abstract [en]

    We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROmaρs efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROmaρs incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROmaρs provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROmaρs for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities.

  • 38.
    Boström, Mathias
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics .
    Williams, DRM
    Ninham, BW
    Special ion effects: Why the properties of lysozyme in salt solutions follow a Hofmeister series2003In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 85, no 2, p. 686-694Article in journal (Refereed)
    Abstract [en]

    Protein solubility in aqueous solutions depends in a complicated and not well understood way on pH, salt type, and salt concentration. Why for instance does the use of two different monovalent salts, potassium thiocyanate and potassium chloride, produce such different results? One important and previously neglected source of ion specificity is the ionic dispersion potential that acts between each ion and the protein. This attractive potential is found to be much stronger for SCN- than it is for Cl-. We present model calculations, performed within a modified ion-specific double-layer theory, that demonstrate the large effect of including these ionic dispersion potentials. The results are consistent with experiments performed on hen egg-white lysozymes and on neutral black lipid membranes. The calculated surface pH and net lysozyme charge depend strongly on the choice of anion. We demonstrate that the lysozyme net charge is larger, and the corresponding Debye length shorter, in a thiocyanate salt solution than in a chloride salt solution. Recent experiments have suggested that pK(a) values of histidines depend on salt concentration and on ionic species. We finally demonstrate that once ionic dispersion potentials are included in the theory these results can quantitatively be reinterpreted in terms of a highly specific surface pH (and a salt-independent pK(a)).

  • 39.
    Brandt, Erik G.
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
    Braun, Anthony R.
    Sachs, Jonathan N.
    Nagle, John F.
    Edholm, Olle
    KTH, School of Engineering Sciences (SCI), Theoretical Physics.
    Interpretation of Fluctuation Spectra in Lipid Bilayer Simulations2011In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 100, no 9, p. 2104-2111Article in journal (Refereed)
    Abstract [en]

    Atomic resolution and coarse-grained simulations of dimyristoylphosphatidylcholine lipid bilayers were analyzed for fluctuations perpendicular to the bilayer using a completely Fourier-based method. We find that the fluctuation spectrum of motions perpendicular to the bilayer can be decomposed into just two parts: 1), a pure undulation spectrum proportional to q(-4) that dominates in the small-q regime; and 2), a molecular density structure factor contribution that dominates in the large-q regime. There is no need for a term proportional to q(-2) that has been postulated for protrusion fluctuations and that appeared to have been necessary to fit the spectrum for intermediate q. We suggest that earlier reports of such a term were due to the artifact of binning and smoothing in real space before obtaining the Fourier spectrum. The observability of an intermediate protrusion regime from the fluctuation spectrum is discussed based on measured and calculated material constants.

  • 40.
    Brandt, Erik G.
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics.
    Edholm, Olle
    KTH, School of Engineering Sciences (SCI), Theoretical Physics.
    Dynamic structure factors from lipid membrane molecular dynamics simulations2009In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 96, no 5, p. 1828-1838Article in journal (Refereed)
    Abstract [en]

    Dynamic structure factors for a lipid bilayer have been calculated from molecular dynamics simulations. From trajectories of a system containing 1024 lipids we obtain wave vectors down to 0.34 nm(-1), which enables us to directly resolve the Rayleigh and Brillouin lines of the spectrum. The results confirm the validity of a model based on generalized hydrodynamics, but also improves the line widths and the position of the Brillouin lines. The improved resolution shows that the Rayleigh line is narrower than in earlier studies, which corresponds to a smaller thermal diffusivity. From a detailed analysis of the power spectrum, we can, in fact, distinguish two dispersive contributions to the elastic scattering. These translate to two exponential relaxation processes in separate time domains. Further, by including a first correction to the wave-vector-dependent position of the Brillouin lines, the results agree favorably to generalized hydrodynamics even up to intermediate wave vectors, and also yields a 20% higher adiabatic sound velocity. The width of the Brillouin lines shows a linear, not quadratic, dependence to low wave vectors.

  • 41.
    Brandt, Erik G.
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
    Edholm, Olle
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
    Molecular Dynamics Simulations of In-Plane Density Fluctuations in Phospholipid Bilayers2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, no 3, p. 664A-664AArticle in journal (Other academic)
  • 42. Braun, Anthony R.
    et al.
    Brandt, Erik G.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical Biological Physics.
    Edholm, Olle
    KTH, School of Engineering Sciences (SCI), Theoretical Physics.
    Nagle, John F.
    Sachs, Jonathan N.
    Determination of Electron Density Profiles and Area from Simulations of Undulating Membranes2011In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 100, no 9, p. 2112-2120Article in journal (Refereed)
    Abstract [en]

    The traditional method for extracting electron density and other transmembrane profiles from molecular dynamics simulations of lipid bilayers fails for large bilayer systems, because it assumes a flat reference surface that does not take into account long wavelength undulations. We have developed what we believe to be a novel set of methods to characterize these undulations and extract the underlying profiles in the large systems. Our approach first obtains an undulation reference surface for each frame in the simulation and subsequently isolates the long-wavelength undulations by filtering out the intrinsic short wavelength modes. We then describe two methods to obtain the appropriate profiles from the undulating reference surface. Most combinations of methods give similar results for the electron density profiles of our simulations of 1024 DMPC lipids. From simulations of smaller systems, we also characterize the finite size effect related to the boundary conditions of the simulation box. In addition, we have developed a set of methods that use the undulation reference surface to determine the true area per lipid which, due to undulations, is larger than the projected area commonly reported from simulations.

  • 43. Briones, Rodolfo
    et al.
    Biau, Christian
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kutzner, Carsten
    de Groot, Bert L.
    Aponte-Santamaria, Camilo
    GROma rho s: A GROMACS-Based Toolset to Analyze Density Maps Derived from Molecular Dynamics Simulations2019In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 116, no 1, p. 4-11Article in journal (Refereed)
    Abstract [en]

    We introduce a computational toolset, named GROma rho s, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROma rho s efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROma rho s incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROma rho s provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROma rho s for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities.

  • 44.
    Brorsson, Ann-Christin
    et al.
    University of Cambridge.
    Bolognesi, Benedetta
    University of Cambridge.
    Tartaglia, Gian Gaetano
    University of Cambridge.
    Shammas, Sarah L
    University of Cambridge.
    Favrin, Giorgio
    University of Cambridge.
    Watson, Ian
    University of Cambridge.
    Lomas, David A
    University of Cambridge.
    Chiti, Fabrizio
    Università degli Studi di Firenze, Italy.
    Vendruscolo, Michele
    University of Cambridge.
    Dobson, Christopher M
    University of Cambridge.
    Crowther, Damian C
    University of Cambridge.
    Luheshi, Leila M
    University of Cambridge.
    Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, no 8, p. 1677-84Article in journal (Refereed)
    Abstract [en]

    The extent to which proteins aggregate into distinct structures ranging from prefibrillar oligomers to amyloid fibrils is key to the pathogenesis of many age-related degenerative diseases. We describe here for the Alzheimer's disease-related amyloid beta peptide (Abeta) an investigation of the sequence-based determinants of the balance between the formation of prefibrillar aggregates and amyloid fibrils. We show that by introducing single-point mutations, it is possible to convert the normally harmless Abeta40 peptide into a pathogenic species by increasing its relative propensity to form prefibrillar but not fibrillar aggregates, and, conversely, to abolish the pathogenicity of the highly neurotoxic E22G Abeta42 peptide by reducing its relative propensity to form prefibrillar species rather than mature fibrillar ones. This observation can be rationalized by the demonstration that whereas regions of the sequence of high aggregation propensity dominate the overall tendency to aggregate, regions with low intrinsic aggregation propensities exert significant control over the balance of the prefibrillar and fibrillar species formed, and therefore play a major role in determining the neurotoxicity of the Abeta peptide.

  • 45.
    Börjesson, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Hammarström, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids2008In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 95, no 5, p. 2242-2253Article in journal (Refereed)
    Abstract [en]

    Polyunsaturated fatty acids (PUFAs) have beneficial effects on epileptic seizures and cardiac arrhythmia. We report that ω-3 and ω-6 all-cis-PUFAs affected the voltage dependence of the Shaker K channel by shifting the conductance versus voltage and the gating charge versus voltage curves in negative direction along the voltage axis. Uncharged methyl esters of the PUFAs did not affect the voltage dependence, whereas changes of pH and charge mutations on the channel surface affected the size of the shifts. This suggests an electrostatic effect on the channel's voltage sensors. Monounsaturated and saturated fatty acids, as well as trans-PUFAs did not affect the voltage dependence. This suggests that fatty acid tails with two or more cis double bonds are required to place the negative carboxylate charge of the PUFA in a position to affect the channel's voltage dependence. We propose that charged lipophilic compounds could play a role in regulating neuronal excitability by electrostatically affecting the channel's voltage sensor. We believe this provides a new approach for pharmacological treatment that is voltage sensor pharmacology. © 2008 by the Biophysical Society.

  • 46.
    Börjesson, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Parkkari, Teija
    University of Kuopio, Finland.
    Hammarström, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Electrostatic Tuning of Cellular Excitability2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, no 3, p. 396-403Article in journal (Refereed)
    Abstract [en]

    Voltage-gated ion channels regulate the electric activity of excitable tissues, such as the heart and brain. Therefore, treatment for conditions of disturbed excitability is often based on drugs that target ion channels. In this study of a voltage-gated K channel, we propose what we believe to be a novel pharmacological mechanism for how to regulate channel activity. Charged lipophilic substances can tune channel opening, and consequently excitability, by an electrostatic interaction with the channels voltage sensors. The direction of the effect depends on the charge of the substance. This was shown by three compounds sharing an arachiclonyl backbone but bearing different charge: arachidonic acid, methyl arachidonate, and arachidonyl amine. Computer simulations of membrane excitability showed that small changes in the voltage dependence of Na and K channels have prominent impact on excitability and the tendency for repetitive firing. For instance, a shift in the voltage dependence of a K channel with -5 or +5 mV corresponds to a threefold increase or decrease in K channel density, respectively. We suggest that electrostatic tuning of ion channel activity constitutes a novel and powerful pharmacological approach with which to affect cellular excitability.

  • 47. Caballero-Herrera, A
    et al.
    Nordstrand, Kerstin
    Södertörn University, School of Life Sciences.
    Berndt, Kurt D
    Södertörn University, School of Life Sciences. Karolinska Institutet.
    Nilsson, L
    Effect of urea on peptide conformation in water: Molecular dynamics and experimental characterization2005In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 89, no 2, p. 842-857Article in journal (Refereed)
    Abstract [en]

    Molecular dynamics simulations of a ribonuclease A C-peptide analog and a sequence variant were performed in water at 277 and 300 K and in 8 M urea to clarify the molecular denaturation mechanism induced by urea and the early events in protein unfolding. Spectroscopic characterization of the peptides showed that the C-peptide analog had a high alpha-helical content, which was not the case for the variant. In the simulations, interdependent side-chain interactions were responsible for the high stability of the alpha-helical C-peptide analog in the different solvents. The other peptide displayed alpha-helical unwinding that propagated cooperatively toward the N-terminal. The conformations sampled by the peptides depended on their sequence and on the solvent. The ability of water molecules to form hydrogen bonds to the peptide as well as the hydrogen bond lifetimes increased in the presence of urea, whereas water mobility was reduced near the peptide. Urea accumulated in excess around the peptide, to which it formed long-lived hydrogen bonds. The unfolding mechanisms induced by thermal denaturation and by urea are of a different nature, with urea-aqueous solutions providing a better peptide solvation than pure water. Our results suggest that the effect of urea on the chemical denaturation process involves both the direct and indirect mechanisms.

  • 48.
    Caban, Kelvin
    et al.
    Columbia Univ, Dept Chem, New York, NY 10027 USA..
    Pavlov, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Kaledhonkar, Sandip
    Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA..
    Fu, Ziao
    Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA..
    Frank, Joachim
    Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.;Columbia Univ, Dept Biol Sci, New York, NY 10027 USA..
    Ehrenberg, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology.
    Gonzalez, Ruben L., Jr.
    Columbia Univ, Dept Chem, New York, NY 10027 USA..
    The Structural Basis for Initiation Factor 2 Activation during Translation Initiation2018In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 3, p. 593A-593AArticle in journal (Other academic)
  • 49.
    Carlsson, Uno
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Hammarström, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Lindgren, M
    Persson, M
    Freskgård, Per-Ola
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Mårtensson, Lars-Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Andersson, D
    Jonsson, Bengt-Harald
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology .
    Svensson, Magdalena
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Aggregation is site-specific in carbonic anhydrase and is prevented by GroEL: The interaction leads to a more flexible structure of both the protein substrate and the chaperonin.2000In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 78, no 1, p. 202Pos-Conference paper (Other academic)
  • 50. Chamberlain, Aaron K
    et al.
    MacPhee, Cait E
    Zurdo, Jesús
    Morozova-Roche, Ludmilla A
    Oxford Centre for Molecular Sciences, New Chemistry Laboratory, University of Oxford.
    Hill, H Allen O
    Dobson, Christopher M
    Davis, Jason J
    Ultrastructural organization of amyloid fibrils by atomic force microscopy2000In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 79, no 6, p. 3282-3293Article in journal (Refereed)
    Abstract [en]

    Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR(10-19) fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.

1234567 1 - 50 of 316
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf