Current Address: Department of Bioengineering, University ofCalifornia, Berkeley, CA
Department of Mechanical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge,MA
Department of Mechanical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA 02139, Email: rdkamm@mit.edu
Abstract:
Membrane-bound integrin receptors are linked to intracellular signaling pathways through focal adhesion kinase (FAK). FAK tends to colocalize with integrin receptors at focal adhesions through its C-terminal focal adhesion targeting (FAT) domain. Through recruitment and binding of intracellular proteins, FAs transduce signals between the intracellular and extracellular regions that regulate a variety of cellular processes including cell migration, proliferation, apoptosis and detachment from the ECM. The mechanism of signaling through the cell is of interest, especially the transmission of mechanical forces and subsequent transduction into biological signals. One hypothesis relates mechanotransduction to conformational changes in intracellular proteins in the force transmission pathway, connecting the extracellular matrix with the cytoskeleton through FAs. To assess this hypothesis, we performed steered molecular dynamics simulations to mechanically unfold FAT and monitor how force-induced changes in the molecular conformation of FAT affect its binding to paxillin.
