Merging theory and biological experiments in search for mechanisms underlying environmental sensing VIC cell adhesion sites Benny Geiger (Weizmann Inst.)
Cell adhesion to the extracellular matrix is a complex process, regulated by multiple genes, at multiple levels. Cells can differentially sense and respond to diverse chemical signals, defined by the molecular composition of the extracellular matrix, as well as to a variety of physical cues, including external or cytoskeleton-generated forces, surface rigidity, geometry and nano-topography. These structural and signaling activities are executed by multi-molecular protein complexes, known collectively as the integrin adhesome, and consisting of specific receptor molecules, actin-associated molecules, adaptor proteins and signaling molecules. Collectively, these protein ensembles control and integrate the interactions of cells with their environment, and the signaling processes triggered at these adhesion sites (e.g. focal adhesions and podosomes), and regulate their effect on the cell’s behavior and fate. In this presentation, I will describe our attempts to unravel the molecular nano-architecture and functional organization of different types of integrin adhesions. I will particularly focus here on a combination of synthetic approaches for extracellular matrix engineering and advanced approaches for correlated light microscopy, in which the same specimens are examined by fluorescence microscopy and cryo-electron tomography. A critical feature of integrin adhesions; namely, their capacity to respond to chemical and physical “environmental cues,” will be described, and novel results, pointing to mechanical regulation of the molecular dynamics of the adhesion site, will be presented. The results obtained using these novel experimental strategies provide new insights into the structure, dynamics and function of focal adhesions of cultured cells, and elucidation of their molecular organization and roles in matrix adhesion, surface sensing, cytoskeletal assembly and cell migration.