YAP-dependent mechanotransduction is required for proliferation and migration on native-like substrate topography.
Biomaterials
; 115: 155-166, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27889666
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 factor through which fibrous substrate topography influences cell behavior and highlights topography as a key design parameter for engineered biomaterials.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Mecanotransducción Celular
/
Células Endoteliales
/
Proliferación Celular
/
Proteínas Reguladoras de la Apoptosis
/
Matriz Extracelular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomaterials
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos