Denis Wirtz, Ph.D. - Johns Hopkins University - Bioengineering Seminar Series - October 14, 2010 11:00 AM - 12:00 PM, IBB Suddath Room 1128

Abstract:

Focal adhesions are large multi-protein clustered assemblies that form at the basal surface of cells placed on planar dishes which mediate cell signaling, force transduction, and adhesion with the underlying substratum. While much is known about the organization and function of focal adhesion components in 2-D systems, their organization and function in migrating cells within a more physiological three-dimensional (3-D) matrix is largely unknown. Quantitative live-cell microscopy shows that for cells fully embedded in a 3-D matrix focal adhesion proteins, including vinculin, paxillin, talin, -actinin, zyxin, VASP, FAK, and p130Cas, do not cluster into appreciable aggregates, but are diffusively distributed in the cytoplasm of cells. Despite the absence of detectable focal adhesions, focal adhesion proteins still modulate cell motility but in a manner distinct from cells moving on conventional planar substrates. Rather, focal adhesion proteins in matrix-embedded cells regulate cell speed by affecting protrusion activity and matrix deformation, two processes that play no direct role in controlling 2-D cell speed. This study shows that actively growing membrane protrusions constitute a critical motility/matrix-traction module that drives cell motility in a 3-D matrix. We will discuss the implications of this work in cancer metastasis.