Intercellular Adhesion
Cell surface adhesion proteins are sites of force transmission in tissues. They maintain the organization of all multicellular organisms, regulate cell shape, maintain tissue barriers, and control immune cell surveilance. Cadherins are the biochemical Velcro that hold cells together in all tissues. We focus on how these essential intercellular adhesion proteins, cadherins interact with other proteins at the cell membrane and in the cytosol to regulate cell-cell adhesion, force transduction, and tissue physiology.
Receptor Binding Equilibria at Cell Surfaces
We discovered that cadherin-mediated force transduction at cell-cell adhesions activates growth factor receptor signaling and downstream pathways that regulate proliferation and differentiation. We are exploring the molecular basis of the interactions between cadherins and growth factor receptors, using a novel fluorescence technique FSI-FRET, developed by Kalina Hrisova at Johns Hopkins. These fluorescence measurements quantify the receptor binding stoichiometry and the binding affinities between membrane receptors at the surfaces of live cells. Related studies investigate how cadherin-mediated force transduction regulates cell proliferation and tissue morphogenesis, particularly in the contexts of vascular disease and breast cancer.
Kinetics and Mechanisms of Cell Adhesion
Our lab uses quantitative measurements of cell-cell binding kinetics to determine the molecular mechanisms of intercellular adhesion and molecular organization at intercellular junctions. Single molecule force measurements quantified the strengths of single protein-ligand bonds. These measurements in conjunction with super resolution imaging, protein engineering, and kinetic modeling reveal how adhesion proteins control the assembly and function of the intercellular adhesions, which determine the permeability of barrier tissues such as skin and the vascular endothelium.