Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors.
Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood. We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase-activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.
Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Kshitiz
Maimon E
ME
Hubbi
Eun Hyun
EH
Ahn
John
J
Downey
Junaid
J
Afzal
Deok-Ho
DH
Kim
Sergio
S
Rey
Connie
C
Chang
Arnab
A
Kundu
Gregg L
GL
Semenza
Roselle M
RM
Abraham
Andre
A
Levchenko
D000818:Animals; D051177:Catenins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D004727:Endothelium / Q000166:cytology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D000095002:Delta Catenin
D051177:Catenins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C085379:rho GTPase-activating protein; D000095002:Delta Catenin