A vascular chip for disease-relevant flow shear stress topology

Abstract

Vascular chips have advanced endothelial mechanobiology by enabling controlled responses to hemodynamic cues, yet disease-relevant wall shear stress (WSS) modeling remains limited. Simplified one-dimensional flow shear systems, designed mainly for physiological mechanobiology, miss the topological organization of pathological flow, whereas patient-specific vascular models capture complex hemodynamics but sacrifice generality and imaging compatibility. Here we develop a programmable vascular chip that converts disease-associated WSS topology into a physiologically parameterized experimental input. The device reconstructs a representative pathological shear-topology field on endothelial layer, supports stationary and physiologically paced oscillatory flow modes, and integrates matched unidirectional-shear references within the same chip. Using this system, we show that oscillatory WSS topology destabilizes endothelial monolayers, drives asymmetric collective emergent behaviors, impairs actin-nuclear mechanotransduction, accompanied by nuclear softening and enhanced perinuclear nanoparticle uptake. Integrated live-cell imaging, fluorescence analysis, Brillouin microscopy, and transport assays enable multimodal phenotyping across collective, subcellular mechanical and functional scales. By making disease-relevant WSS topology experimentally controllable, this vascular-chip framework bridges computational hemodynamics and experimental mechanomedicine, supporting standardized vascular disease modeling and functional screening.