Mechanical regulation of cellular phenotype in 3D engineered tissue constructs
Cytoskeletal regulation mechanisms have been strongly linked to the action of mechanical stresses. The overall goal
in this project is to define the mechanisms linking mechanical stress to degenerative change in mitral valves in
vitro. Specifically, we focus on elucidating the mechanotransduction pathways that are initiated at the membrane
mechanoreceptors and act via signaling pathways to regulate α-actin expression.
The central hypothesis is that exposure of porcine mitral valves to pathologic mechanical stresses will increase
levels of α-actin expression through integrin mechanoreceptors and Rho signaling. The rationale for these
studies is that, by understanding the mechanoreceptor and signaling mechanisms mediating in vitro
mechanically-induced degenerative changes, new molecular targets can be established for correction of valvular
dysfunction and will provide the basis for development of novel tissue-engineered valves.
Pulsatile tensile stress applied to tissuesImmunofluorescence of tryptophan hydroxylase 1 showing up-regulation due to the application of tensile
forces. Left image is before application; right is after application.