Cell Adhesion

Tissue development and tumor metastasis are two critical processes in which cell adhesion plays a central role. Cell adhesion provides mechanical linkages to other cells or to matrix, and many adhesion proteins are signaling molecules that transmit mechanical information to the cytosol. Conversely, adhesion dysfunction is causally linked to several diseases such as cancer. How cells (and adhesion proteins) sense and respond to these mechanical signals is an important, but largely unexplored problem in biology.

To address this topic, we use cell mechanical measurements, protein nanomechanics, biomolecular engineering, and molecular modeling. Sensitive force-measuring techniques determine relationships between protein architecture and the nanomechanics of protein-ligand bonds. These biophysical approaches together with protein engineering identified key force transduction elements in protein structures. We are also establishing how the biophysical properties of individual proteins determine the strength and dynamics of adhesion between living cells. These approaches are used to determine molecular pathways that link adhesion proteins to the cytoskeleton and intracellular signaling. We are similarly studying how intracellular signals and cytoskeletal attachments reinforce or destabilize intercellular junctions.