Mind the gap: Size-based signaling at cell-cell contacts

Membrane interfaces formed at junctions between cells are often associated with characteristic patterns of membrane protein organization, such as in epithelial tissues and between cells of the immune system. While this organization can be influenced by receptor clustering, lipid domain formation, and cytoskeletal dynamics, this talk will describe how the size of the gap between two membranes can directly contribute to the spatial arrangement of membrane proteins and resulting cell-cell signaling at membrane interfaces. Using in vitro systems based on giant unilamellar vesicles and live cells of the immune system, we are investigating how fluid membrane interfaces linked by adhesion proteins can drive segregation of non-adhesive proteins and how this segregation can affect macrophage signaling during receptor-mediated target recognition. Results from these studies support a model in which cell surface protein size plays a key role in mediating cell-cell communication and function.