Functional microarray biochips promote micropatterned adhesion-cytoskeleton-nuclear coupling to guide endothelial force-sensing mechanotransduction

Abstract

Microarray biochips offer an advanced platform for the precise spatial control of cell behaviors, enabling the investigation of how geometric constraints influence cell adhesion, morphology, and mechanosensitive signaling. Herein, a microengineered biochip is specifically designed to explore nuclear force-sensing mechanotransduction in human umbilical vein endothelial cells (HUVECs). The patterned substrate facilitates the organized assembly of focal adhesion (FA) nanoarchitectures and cytoskeletal structures by promoting integrin engagement to recruit key scaffolding proteins, including talin, vinculin, and actin filaments, along with myosin. These dynamic interactions between the extracellular matrix (ECM) and cytoskeletal tension form a mechanical interface for promoting efficient signal transduction in nuclei.Moreover, this mechanical interaction enhances the activation of the Piezo1 ion channel, a key sensor of mechanical stress in endothelial cells. Upon activation, Piezo1 induces calcium influx to trigger a cascade of downstream signaling pathways, responsible for cellular response, such as proliferation, migration, and differentiation. The spatial confinement induced by the microarray-patterned biochips significantly amplifies the integrin-cytoskeleton-Piezo1 signaling axis, suggesting that microtopographical cues are critical for modulating nuclear force-sensing mechanotransduction in endothelial cells. This study provides a foundation for mechanically responsive biomaterials and mechanosensing.