Ph.D. Proposal Presentation by Nathan D. Gallant
Friday, October 17, 2003

(Dr. Andrés J. García, advisor)

"Analysis of Integrin-Mediated Cell Adhesion Strengthening Using Surfaces Engineered to Control Cell Shape and Focal Adhesion Assembly"

Abstract

Cell adhesion to extracellular matrix proteins is critical to physiological and pathological processes as well as biomedical and biotechnological applications. Cell adhesion is a highly regulated process involving initial receptor-ligand binding, and subsequent clustering of these receptors and rapid association with the actin cytoskeleton as focal adhesions are assembled. Focal adhesions enhance adhesion, functioning as structural links between the cytoskeleton and the extracellular matrix and triggering signaling pathways that direct cell function. The objective of this proposed thesis research is to develop a mechanical and biochemical analysis of the adhesion strengthening response.

Our central hypothesis is that focal adhesion size and position regulate cell adhesion strength by controlling the distribution of mechanical loading. We will engineer micropatterned surfaces to control the size and position of focal adhesions in order to analyze the contributions of these specialized adhesive structures to adhesion strengthening. By applying surface micropatterning techniques, we show robust control over cell-substrate contact area and focal adhesion assembly. Using a hydrodynamic shear assay to quantify adhesion strength to micropatterned substrates, we expect significant adhesive area- and time-dependent increases in adhesion strength. In addition, we will biochemically examine the structure-function relationships between these adhesive structures and adhesion strength.