Mechanosensitivity of integrin adhesion complexes: role of the consensus adhesome

Abstract

Cell and tissue stiffness have been known to contribute to both developmental and pathological signalling for some time, but the underlying mechanisms remain elusive. Integrins and their associated adhesion signalling complexes (IACs), which form a nexus between the cell cytoskeleton and the extracellular matrix, act as a key force sensing and transducing unit in cells. Accordingly, there has been much interest in obtaining a systems-level understanding of IAC composition. Proteomic approaches have revealed the complexity of IACs and identified a large number of components that are regulated by cytoskeletal force. Here we review the function of the consensus adhesome, an assembly of core IAC proteins that emerged from a meta-analysis of multiple proteomic datasets, in the context of mechanosensing. As IAC components have been linked to a variety of diseases involved with rigidity sensing, the field is now in a position to define the mechanosensing function of individual IAC proteins and elucidate their mechanisms of action.

The integrin adhesome network at a glance

“…Additional analyses such as these might reveal not only context-specific adhesome components but also the number of consensus adhesome components that are conserved between integrin adhesions in different systems. The role of the consensus adhesome in relation to mechanosensation was recently reviewed, and its components were shown to change almost uniformly upon loss of myosin-driven intracellular force (Horton et al, 2016b). Thus, data generated under alternative conditions, such as using differing ECMs, might present a completely different view of the adhesion nexus or consensus adhesome, or increase the number of literature-curated adhesome components identified using mass-spectrometry-based approaches.…”

Osteoblasts preferentially adhere to peaks on micro-structured titanium

“…Cell shape is determined by the complex interaction between cytoskeletal components that regulate the cellular internal structure and the mechanical integration of the cell with the extracellular matrix [12][13][14] . According to the tensional integrity theory, cell shape is maintained through a balance of forces generated by actomyosin filaments and withstood by microtubules, which act like rigid support struts for cells 15) .…”

Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts

“…Proteomics experiments have identified many proteins, including a number with LIM domains, that are preferentially incorporated into more mature adhesions under myosin II-generated tension [15••, 17, 18], so increasing the repertoire of likely proteins involved in mechanotransduction [45, 46]. Particular integrins (for example, α5β1 and αV) selectively recruit proteins that mediate differential responses to force, indicating that receptor-specific and multiple modes of rigidity sensing exist [20].…”