Emergent collective behavior of platelets in blood clotting: lessons for designing active polymeric networks

Blood clots play a critical role in restoring hemostasis and regulating thrombosis in the body. Upon vascular injury, a cascade of events culminates in the formation of a soft plug of fibrin fibers and small anucleate blood cells called platelets. Platelets become activated and undergo actomyosin-based contraction with fibrin fibers to shrink the overall clot size, modify clot structure, and mechanically stabilize the clot. We developed an experimentally informed mesoscale computational model of fibrin- platelet blood clots to gain insights into the contraction mechanics of clots and to examine the interactions among different clot elements. The active micromechanics of contracting clots exhibits a remarkable example of design principles that can be adapted for developing active materials. The simulations reveal that platelets utilize a new emergent behavior, triggered by the heterogeneity in the timing of platelet activation, to enhance volumetric material contraction and to magnify contractile forces. We demonstrate the connection between the forces produced by individual platelets nested within fibrin mesh and the macroscopic forces generated by the clot and show how the clot forces depend on network properties. The ability of contracting colts to entrap and retain red blood cells provides a means for controlling clot internal structure and mechanics. While we are still far from being able to synthesize materials that can match the amazing complexity of biological systems, our results provide valuable guidelines for developing advanced synthetic and hybrid materials with platelet- inspired distributed actuation.