A few immobilized thrombins are sufficient for platelet spreading

Yosuke Okamura, Roman Schmidt, Ines Raschke, Maik Hintze, Shinji Takeoka, Alexander Egner, Thorsten Lang

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Eukaryotic cells respond to signaling molecules with picomolar to nanomolar sensitivities. However, molar concentrations give no suggestion of the sufficient number of molecules per cell and are confusing when referring to physiological situations in which signaling molecules act in an immobilized state. Here, we studied platelet adhesion by thrombin, a key step in normal hemostasis and pathological arterial thrombosis. We generated a biofunctional nanosheet surface to mimic the in vivo solid-state interaction between platelets and thrombin at sites of injured tissues. We observed that <10 molecules readily activate platelets with high specificity, resulting in platelet adhesion and spreading. This number is much lower than expected from previous experiments in solution, in which the sole activation of platelets required a >1000-fold stoichiometric excess of thrombin. We conclude that immobilizing thrombin apposed to the membrane receptor allows platelets to respond with very high sensitivity. Moreover, we propose that irreversible cell activation may require several ligands to avoid activation by single, mislocalized signaling molecules.

    Original languageEnglish
    Pages (from-to)1855-1863
    Number of pages9
    JournalBiophysical Journal
    Volume100
    Issue number8
    DOIs
    Publication statusPublished - 2011 Apr 20

      Fingerprint

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    Okamura, Y., Schmidt, R., Raschke, I., Hintze, M., Takeoka, S., Egner, A., & Lang, T. (2011). A few immobilized thrombins are sufficient for platelet spreading. Biophysical Journal, 100(8), 1855-1863. https://doi.org/10.1016/j.bpj.2011.02.052