Platelet Shape Changes during Thrombus Formation: Role of Actin-Based Protrusions

Abstract

Platelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet cytoskeleton is a critical component for proper hemostatic function. Platelets change their shape after activation and their contractile machinery mediates thrombus stabilization and clot retraction. In vitro studies have shown that platelets, which come into contact with proteins such as fibrinogen, spread and first form filopodia and then lamellipodia, the latter being plate-like protrusions with branched actin filaments. However, the role of platelet lamellipodia in hemostasis and thrombus formation has been unclear until recently. This short review will briefly summarize the recent findings on the contribution of the actin cytoskeleton and lamellipodial structures to platelet function.

Keywords

platelet - thrombus - cytoskeleton - lamellipodia - actin

Publikationsverlauf

Eingereicht: 13. Oktober 2020

Angenommen: 28. November 2020

Artikel online veröffentlicht:
15. Februar 2021

• References

• 1 Nieswandt B, Pleines I, Bender M. Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J Thromb Haemost 2011; 9 (Suppl. 01) 92-104
• 2 Vögtle T, Cherpokova D, Bender M, Nieswandt B. Targeting platelet receptors in thrombotic and thrombo-inflammatory disorders. Hamostaseologie 2015; 35 (03) 235-243
• 3 Swieringa F, Baaten CC, Verdoold R. et al. Platelet control of fibrin distribution and microelasticity in thrombus formation under flow. Arterioscler Thromb Vasc Biol 2016; 36 (04) 692-699
• 4 Falet H. Anatomy of the platelet cytoskeleton. In: Gresele P, Kleiman NS, Lopez JA, Page CP. eds. Platelets in Thrombotic and Non-Thrombotic Disorders: Pathophysiology, Pharmacology and Therapeutics: an Update. New York, NY: Springer International Publishing AG; 2017: 139-156
• 5 Thomas SG. The structure of resting and activated platelets. In: Michelson AD. ed. Platelets. 4th ed.. Cambridge, MA: Elsevier; 2019: 47-77
• 6 Hartwig JH, DeSisto M. The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and its attachment to actin filaments. J Cell Biol 1991; 112 (03) 407-425
• 7 Patel-Hett S, Wang H, Begonja AJ. et al. The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation. Blood 2011; 118 (06) 1641-1652
• 8 Italiano Jr JE, Bergmeier W, Tiwari S. et al. Mechanisms and implications of platelet discoid shape. Blood 2003; 101 (12) 4789-4796
• 9 Steiner M, Ikeda Y. Quantitative assessment of polymerized and depolymerized platelet microtubules. Changes caused by aggregating agents. J Clin Invest 1979; 63 (03) 443-448
• 10 Diagouraga B, Grichine A, Fertin A, Wang J, Khochbin S, Sadoul K. Motor-driven marginal band coiling promotes cell shape change during platelet activation. J Cell Biol 2014; 204 (02) 177-185
• 11 Sadoul K. New explanations for old observations: marginal band coiling during platelet activation. J Thromb Haemost 2015; 13 (03) 333-346
• 12 Dmitrieff S, Alsina A, Mathur A, Nédélec FJ. Balance of microtubule stiffness and cortical tension determines the size of blood cells with marginal band across species. Proc Natl Acad Sci U S A 2017; 114 (17) 4418-4423
• 13 Hartwig J, Italiano Jr J. The birth of the platelet. J Thromb Haemost 2003; 1 (07) 1580-1586
• 14 Hartwig JH. The platelet: form and function. Semin Hematol 2006; 43 (01) (Suppl. 01) S94-S100
• 15 Cerecedo D. Platelet cytoskeleton and its hemostatic role. Blood Coagul Fibrinolysis 2013; 24 (08) 798-808
• 16 Qiu Y, Ciciliano J, Myers DR, Tran R, Lam WA. Platelets and physics: how platelets “feel” and respond to their mechanical microenvironment. Blood Rev 2015; 29 (06) 377-386
• 17 Weisel JW. Biophysics. Enigmas of blood clot elasticity. Science 2008; 320 (5875): 456-457
• 18 Kim OV, Litvinov RI, Alber MS, Weisel JW. Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nat Commun 2017; 8 (01) 1274
• 19 Myers DR, Qiu Y, Fay ME. et al. Single-platelet nanomechanics measured by high-throughput cytometry. Nat Mater 2017; 16 (02) 230-235
• 20 Ting LH, Feghhi S, Taparia N. et al. Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk. Nat Commun 2019; 10 (01) 1204
• 21 Otto O, Rosendahl P, Mietke A. et al. Real-time deformability cytometry: on-the-fly cell mechanical phenotyping. Nat Methods 2015; 12 (03) 199-202 , 4, 202
• 22 Scheller I, Stritt S, Beck S. et al. Coactosin-like 1 integrates signaling critical for shear-dependent thrombus formation in mouse platelets. Haematologica 2020; 105 (06) 1667-1676
• 23 Aurich K, Fregin B, Palankar R. et al. Label-free on chip quality assessment of cellular blood products using real-time deformability cytometry. Lab Chip 2020; 20 (13) 2306-2316
• 24 Ciciliano JC, Tran R, Sakurai Y, Lam WA. The platelet and the biophysical microenvironment: lessons from cellular mechanics. Thromb Res 2014; 133 (04) 532-537
• 25 Feghhi S, Sniadecki NJ. Mechanobiology of platelets: techniques to study the role of fluid flow and platelet retraction forces at the micro- and nano-scale. Int J Mol Sci 2011; 12 (12) 9009-9030
• 26 Zaninetti C, Sachs L, Palankar R. Role of platelet cytoskeleton in platelet biomechanics: current and emerging methodologies and their potential relevance for the investigation of inherited platelet disorders. Hamostaseologie 2020; 40 (03) 337-347
• 27 Sachs L, Denker C, Greinacher A, Palankar R. Quantifying single-platelet biomechanics: an outsider's guide to biophysical methods and recent advances. Res Pract Thromb Haemost 2020; 4 (03) 386-401
• 28 Hartwig JH. Mechanisms of actin rearrangements mediating platelet activation. J Cell Biol 1992; 118 (06) 1421-1442
• 29 Falet H, Hoffmeister KM, Neujahr R. et al. Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts. Proc Natl Acad Sci U S A 2002; 99 (26) 16782-16787
• 30 Campellone KG, Welch MD. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 2010; 11 (04) 237-251
• 31 Poulter NS, Pollitt AY, Davies A. et al. Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex. Nat Commun 2015; 6: 7254
• 32 Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood 2002; 100 (06) 2113-2122
• 33 Schurr Y, Sperr A, Volz J. et al. Platelet lamellipodium formation is not required for thrombus formation and stability. Blood 2019; 134 (25) 2318-2329
• 34 Derivery E, Lombard B, Loew D, Gautreau A. The Wave complex is intrinsically inactive. Cell Motil Cytoskeleton 2009; 66 (10) 777-790
• 35 McCarty OJ, Larson MK, Auger JM. et al. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J Biol Chem 2005; 280 (47) 39474-39484
• 36 Pleines I, Elvers M, Strehl A. et al. Rac1 is essential for phospholipase C-gamma2 activation in platelets. Pflugers Arch 2009; 457 (05) 1173-1185
• 37 Paul DS, Casari C, Wu C. et al. Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice. Blood Adv 2017; 1 (18) 1398-1408
• 38 Agbani EO, van den Bosch MT, Brown E. et al. Coordinated membrane ballooning and procoagulant spreading in human platelets. Circulation 2015; 132 (15) 1414-1424
• 39 Krause M, Gautreau A. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat Rev Mol Cell Biol 2014; 15 (09) 577-590
• 40 Gaertner F, Ahmad Z, Rosenberger G. et al. Migrating platelets are mechano-scavengers that collect and bundle bacteria. Cell 2017; 171 (06) 1368.e23-1382.e23
• 41 Nicolai L, Schiefelbein K, Lipsky S. et al. Vascular surveillance by haptotactic blood platelets in inflammation and infection. Nat Commun 2020; 11 (01) 5778
• 42 Gupta S, Konradt C, Corken A. et al. Hemostasis vs. homeostasis: platelets are essential for preserving vascular barrier function in the absence of injury or inflammation. Proc Natl Acad Sci U S A 2020; 117 (39) 24316-24325