Adhesion Protein Architecture and Intermembrane Potentials: Force Measurements and Biological Significance

This chapter focuses on novel relationships between the architectures of large, multi-domain adhesion proteins and the functional importance of these complex structures in controlling interactions between cell membranes. The primary focus is on adhesion proteins with complex extracellular regions. Intrinsically disordered proteins (IDPs) are also discussed as an example of a molecular strategy that enables membrane proteins to interact over large distances. Many of the proteins described in this chapter function at buried interfaces, and the functional significance of protein structures is not easily determined with standard biochemical measurements. Consequently, this chapter highlights different experimental approaches that assess protein functions in confined environments. Several examples emphasize the molecular force measurements of protein-mediated membrane interactions, but they also include measurements of cell binding kinetics, which are used to determine macromolecular binding mechanisms. The physiological significance of these findings is discussed in the context of the different examples.