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 tissues

Immunofluorescence of tryptophan hydroxylase 1 showing up-regulation due to the application of tensile forces. Left image is before application; right is after application.