2018
DOI: 10.1038/s41598-018-23684-w
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Morphometric analysis of spread platelets identifies integrin αIIbβ3-specific contractile phenotype

Abstract: Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro, we developed a morphometric screen to quantify the spatial organization of actin fibres and vinculin adhesion sites in single spread platelets. Platelets from healthy donors predominantly adopted a bipolar morphology on fibrinogen and… Show more

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Cited by 34 publications
(60 citation statements)
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“…Notably, a previous TFM-based study of platelet tension found that mild alignment established immediately upon platelet spreading and subsequently remained constant 58 (e.g., the first and third phases described above occur coincidentally). However, the discrepancy between that study and our results may have resulted from a difference in substrate stiffness (a recent super-resolution study of actin organization showed that alignment of the actin cytoskeleton along an axis was more prominent on stiffer substrates 59 ), the lower spatial resolution of TFM, or differences in the identity and/or surface density of our ligands.…”
Section: Time-lapse Imaging Of Platelets Force Alignmentcontrasting
confidence: 96%
See 3 more Smart Citations
“…Notably, a previous TFM-based study of platelet tension found that mild alignment established immediately upon platelet spreading and subsequently remained constant 58 (e.g., the first and third phases described above occur coincidentally). However, the discrepancy between that study and our results may have resulted from a difference in substrate stiffness (a recent super-resolution study of actin organization showed that alignment of the actin cytoskeleton along an axis was more prominent on stiffer substrates 59 ), the lower spatial resolution of TFM, or differences in the identity and/or surface density of our ligands.…”
Section: Time-lapse Imaging Of Platelets Force Alignmentcontrasting
confidence: 96%
“…We and others previously observed alignment of platelet contractile forces along an axis (or three or more axes all pointing inward) via MFM 16 , TFM 51,58 , DNA tension gauge tether studies with complementary imaging of focal adhesion protein vinculin 52 , and super-resolution and electron microscopy of cytoskeletal filaments and vinculin 59 . However, our work here represents, to the best of our knowledge, the first observation of alignment as a dynamic process, raising questions about the biophysical mechanisms underpinning this phenomenon.…”
Section: Time-lapse Imaging Of Platelets Force Alignmentmentioning
confidence: 88%
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“…Unlike EM techniques, these samples can be prepared using regular biochemical processes that preserve biological functions. Amongst many nanoscopic techniques, Structured Illumination Microscopy (SIM) and Single Molecule Localization Microscopy (SMLM) approaches (61) have provided unique insights into cytoskeletal protein clusters of actin nodules (65), tubulin and actin stress fibers (96,97), and cytoskeletal rearrangement during platelet activation (98,99). These approaches also have greatly improved knowledge of surface receptor co-localizations.…”
Section: Nanoscale Imaging Of Single Plateletsmentioning
confidence: 99%