3D micropattern force triggers YAP nuclear entry by transport across nuclear pores and modulates stem cells paracrine

Abstract Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction. However, it is still unclear that how cells sense and transduce mechanical signals from 3D geometry to regulate function. Here, mechanotransduction human mesenchymal stem (MSCs) triggered micropattern its effect on paracrine MSCs are systematically investigated. Our findings show micropatterns could spatial reorganization cytoskeleton, leading different local forces which mediate nucleus alteration such as orientation, morphology, expression Lamin A/C chromatin condensation. Specifically, in triangular prism cuboid micropatterns, ordered F-actin fibers distribute over fully transmit compressive nucleus, results nuclear flattening stretching pores, thus enhancing import YES-associated protein (YAP). Furthermore, activation YAP significantly enhances upregulates secretion angiogenic growth factors. In contrast, fewer cylinder cube cause less entering nucleus. The skin repair experiment provides first vivo evidence enhanced promotes tissue regeneration. current study contributes understand indepth mechanisms affecting function inspiration for biomaterials design.