Cell adhesion to extracellular matrices (ECM) is essential to numerous physiological and pathological processes. Cell adhesion is initiated by binding of the transmembrane integrin family of receptors to an ECM ligand such as fibronectin (FN). Once bound, integrins cluster together and form focal adhesions (FA). FAs serve as structural links and signal transduction elements between the cell and its extracellular environment. While a great deal of progress has been made in identifying the biochemical components that comprise focal adhesions and the roles they play in migration, cell spreading, and signaling, the contributions of these proteins to mechanical interactions between the cell and its environment remain poorly understood.

A FA adhesion protein of particular importance is vinculin. When localized to focal adhesions, vinculin forms a ternary complex with talin and β1-integrin. This β1-integrin-talin-vinculin complex plays a central role in the regulation of FA assembly and cell spreading and migration. Nevertheless, the specific contribution to adhesive force generation of the β1-integrin-talin-vinculin complex remains poorly understood.

The objective of this project was to analyze the role of vinculin in the cell adhesion strengthening process. Our central hypothesis is that vinculin modulates adhesion strength via regulating the size and/or composition of the integrin-talin-vinculin complex. We used a novel combination of biochemical reagents and engineering techniques along with quantitative and sensitive adhesion strength measurements to provide new insights into how the structure of vinculin contributes to cell adhesion strength.