Fluorescence Nanoscopy of Platelets Resolves Platelet-State Specific Storage, Release and Uptake of Proteins, Opening up Future Diagnostic Applications
2012 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 1, no 6, 707-713 p.Article in journal (Refereed) Published
Dysregulation of how platelets store, sequester and release specific proteins seems to be implicated in many disease states, including cancer. Dual-color immunofluorescence stimulated emission depletion (STED) microscopy with 40 nm resolution is used to map pro-angiogenic VEGF, anti-angiogenic PF-4 and fibrinogen in >300 individual platelets. This reveals that these proteins are stored in a segmented, zonal manner within regional clusters, significantly smaller than the size of an alpha-granule. No colocalization between the different proteins is observed. Upon platelet activation by thrombin or ADP, the proteins undergo significant spatial rearrangements, including alterations in the size and number of the protein clusters, and specific for a certain protein and the type of activation induced. Following these observations, a simple assignment procedure is used to show that the three distinct states of platelets (non-, ADP- and thrombin-activated) can be identified based on the average size, number and peripheral localization profiles of the regional protein clusters within the platelets. Thus, high-resolution spatial mapping of specific proteins is a useful procedure to detect and characterize deviations in the selective storage, release and uptake of these proteins in the platelets. Since these deviations seem to be specific for, and may even underlie, certain patophysiological states, these findings may have interesting diagnostic and therapeutic implications.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2012. Vol. 1, no 6, 707-713 p.
Alpha-Granules, Sted Microscopy, Angiogenesis, Resolution, Reveals, Probes
Biophysics Cell Biology
Research subject Biological Physics
IdentifiersURN: urn:nbn:se:kth:diva-119425DOI: 10.1002/adhm.201200172ISI: 000315120500003ScopusID: 2-s2.0-84879608714OAI: oai:DiVA.org:kth-119425DiVA: diva2:611046
FunderSwedish Research Council, VR-2006-3197Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 201303142013-03-142013-03-142016-03-10Bibliographically approved