Overview

We study how cell-matrix adhesion sites (Fig. 1) are assembled, regulated and function. Fundamental challenges for understanding these processes arise from the large number of adhesion site components and the complex interactions between them (Fig. 2). To comprehensively cope with this complexity, we develop diverse imaging and systems biology approaches. By applying these approaches for different cellular contexts, we gain insights about principles governing cell-matrix adhesion.

Figure 1. Cell-matrix adhesion sites. Cell-matrix adhesion is mediated by dynamic and diverse sites along the plasma membrane at which transmembrane receptors of the integrin family anchor the actin cytoskeleton to components of the extracellular matrix via a multi-protein structure. The scheme is modified from Hoffmann et al., eLife 3:e02257 (2014).

Figure 2. The integrin adhesome. More than 100 different proteins, collectively termed the integrin adhesome, were found to be localized in cell-matrix adhesion sites. These proteins are interconnected by a dense network of regulated interactions (edges). The integrin adhesome network is shown here divided into structural (center) and regulatory/signalling (left and right) sub-networks. The structural part consists of actin, integrins (ITGA, ITGB) and other adhesion receptors (light brown ellipses), cytoskeletal proteins (cyan ellipses), actin modulators (light green) and multi-domain adaptor proteins (red). The regulatory/signaling part includes small GTPases and their regulators, diverse kinases and phosphatases and others. Reproduced from: Zamir and Geiger, "Focal Adhesions and Related Integrin Contacts", In: Encyclopedia of Biological Chemistry (Second Edition), Elsevier, Oxford. 2:318-323 (2013).