Platelets respond dynamically to a wide range of mechanical forces in the bloodstream. This chapter examines how flow-based assays have illuminated the mechanisms of platelet adhesion, activation, and aggregation under diverse (patho)physiologic flows. We begin with a historical overview, tracing the evolution from annular and parallel-plate flow chambers to modern microfluidic platforms and rheometers. These systems have revealed that distinct shear stress regimes elicit unique platelet behaviors, emphasizing the need to carefully model arterial versus venous flows, or even the extreme conditions found in stenoses and mechanical circulatory devices. We then detail the core biophysical parameters relevant to flow-based platelet assays, including shear stress, elongational flow, and the impact of channel geometry on platelet adhesion. Key discoveries in von Willebrand factor-mediated adhesion and shear-induced platelet activation underscore the interplay between fluid mechanics and platelet receptor signaling. In parallel, we discuss the advantages and limitations of different flow-based platelet assays. Finally, we explore emerging methods which incorporate vascular cell co-cultures and three-dimensional architectures to more faithfully mimic in vivo blood flow. By recapitulating critical hemodynamic features in controlled laboratory settings, these tools deepen our understanding of platelet function and guide innovative strategies to prevent or treat thrombotic disease.

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Methods for Studying Platelet Function in (Patho)physiologic Flows

  • David L. Bark,
  • Keith B. Neeves

摘要

Platelets respond dynamically to a wide range of mechanical forces in the bloodstream. This chapter examines how flow-based assays have illuminated the mechanisms of platelet adhesion, activation, and aggregation under diverse (patho)physiologic flows. We begin with a historical overview, tracing the evolution from annular and parallel-plate flow chambers to modern microfluidic platforms and rheometers. These systems have revealed that distinct shear stress regimes elicit unique platelet behaviors, emphasizing the need to carefully model arterial versus venous flows, or even the extreme conditions found in stenoses and mechanical circulatory devices. We then detail the core biophysical parameters relevant to flow-based platelet assays, including shear stress, elongational flow, and the impact of channel geometry on platelet adhesion. Key discoveries in von Willebrand factor-mediated adhesion and shear-induced platelet activation underscore the interplay between fluid mechanics and platelet receptor signaling. In parallel, we discuss the advantages and limitations of different flow-based platelet assays. Finally, we explore emerging methods which incorporate vascular cell co-cultures and three-dimensional architectures to more faithfully mimic in vivo blood flow. By recapitulating critical hemodynamic features in controlled laboratory settings, these tools deepen our understanding of platelet function and guide innovative strategies to prevent or treat thrombotic disease.