Arterial Shear Rate Determines the Structure and Mechanical Properties of Whole-Blood Clots

BackgroundArterial thrombosis arises under high shear conditions and is a leading cause of ischemic stroke and myocardial infarction. The local hemodynamic environment during the formation of the thrombus influences its final composition, which in turn influences its mechanical characteristics and the associated risk of embolization. However, how arterial shear rates determine the local mechanical properties, structure and composition of clots remains poorly understood. ObjectiveTo investigate how physiological and pathological arterial shear rates shape blood clot composition, formation dynamics, and regional mechanical properties in a newly-developed microfluidic flow model. MethodsWe used a microfluidic flow model that allows real-time imaging of blood clot formation under controlled arterial shear rates (300, 1000, and 3500s-1). We visualized platelets and fibrin deposition using confocal microscopy and quantified composition-dependent spatial heterogeneities in clot stiffness with microindentation. ResultsPathologically high (3500 s-1) arterial shear rates promoted more rapid platelet aggregation and the formation of taller platelet-rich clots. Fibrin deposition started after about 6 minutes in all shear conditions and coincided with platelet aggregate stabilization at higher shear rates. Microindentation revealed that platelet- and fibrin-rich regions were significantly stiffer than red blood cell-rich regions. Clots formed at 3500s-1 had a > 3-fold higher average stiffness than those formed at 300s-1, reflecting their higher platelet content. ConclusionsThis study demonstrates that arterial shear rate governs clot growth and composition, translating into shear-dependent microscale mechanical properties. These findings provide new mechanistic insights into clot properties that are relevant for clot stability and vulnerability to embolization.