YAP-dependent mechanotransduction is required for proliferation and migration on native-like substrate topography.

ABSTRACT: Native vascular extracellular matrices (vECM) consist of elastic fibers that impart varied topographical properties, yet most in vitro models designed to study the effects of topography on cell behavior are not representative of native architecture. Here, we engineer an electrospun elastin-like protein (ELP) system with independently tunable, vECM-mimetic topography and demonstrate that increasing topographical variation causes loss of endothelial cell-cell junction organization. This loss of VE-cadherin signaling and increased cytoskeletal contractility on more topographically varied ELP substrates in turn promote YAP activation and nuclear translocation, resulting in significantly increased endothelial cell migration and proliferation. Our findings identify YAP as a required signaling fa

SUBMITTER: Mascharak S 

PROVIDER: S-EPMC5572766 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature