Differential dynamics of early stages of platelet adhesion and spreading on collagen IV and fibrinogen-coated surfaces [version 2; peer review: 3 approved]

Melanie B. Horev, Yishaia Zabary, Revital Zarka, Simona Sorrentino, Ohad Medalia, Assaf Zaritsky, Benjamin Geiger

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Upon wound formation, platelets adhere to the neighboring extracellular matrix and spread on it, a process which is critical for physiological wound healing. Multiple external factors, such as the molecular composition of the environment and its mechanical properties, play a key role in this process and direct its speed and outcome. Methods: We combined live cell imaging, quantitative interference reflection microscopy and cryo-electron tomography to characterize, at a single platelet level, the differential spatiotemporal dynamics of the adhesion process to fibrinogen and collagen IV-functionalized surfaces. Results: Initially, platelets sense both substrates by transient rapid extensions of filopodia. On collagen IV, a short-term phase of filopodial extension is followed by lamellipodia-based spreading. This transition is preceded by the extension of a single or couple of microtubules into the platelet’s periphery and their apparent insertion into the core of the filopodia. On fibrinogen surfaces, the filopodia-tolamellipodia transition was partial and microtubule extension was not observed leading to limited spreading, which could be restored by manganese or thrombin. Conclusions: Based on these results, we propose that interaction with collagen IV stimulate platelets to extend microtubules to peripheral filopodia, which in turn, enhances filopodial-to-lamellipodial transition and overall lamellipodia-based spreading. Fibrinogen, on the other hand, fails to induce these early microtubule extensions, leading to full lamellipodia spreading in only a fraction of the seeded platelets. We further suggest that activation of integrin αIIbβ3 is essential for filopodial-to-lamellipodial transition, based on the capacity of integrin activators to enhance lamellipodia spreading on fibrinogen.

Original languageEnglish
Pages (from-to)1-27
Number of pages27
JournalF1000Research
Volume9
DOIs
StatePublished - 1 Jan 2021

Keywords

  • Fibrinogen
  • Integrin αIIbβ3
  • Interference Reflection Microscopy (IRM)
  • Live cell imaging
  • Microtubules
  • Platelet spreading
  • Type IV collagen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Pharmacology, Toxicology and Pharmaceutics (all)

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