Protein conformation as a regulator of cell–matrix adhesion

Abstract

The dynamic regulation of cell-matrix adhesion is essential for tissue homeostasis and architecture, and thus numerous pathologies are linked to altered cell-extracellular matrix (ECM) interaction and ECM scaffold. The molecular machinery involved in cell-matrix adhesion is complex and involves both sensory and matrix-remodelling functions. In this review, we focus on how protein conformation controls the organization and dynamics of cell-matrix adhesion. The conformational changes in various adhesion machinery components are described, including examples from ECM as well as cytoplasmic proteins. The discussed mechanisms involved in the regulation of protein conformation include mechanical stress, posttranslational modifications and allosteric ligand-binding. We emphasize the potential role of intrinsically disordered protein regions in these processes and discuss the role of protein networks and co-operative protein interactions in the formation and consolidation of cell-matrix adhesion and extracellular scaffolds.

Integrin-independent Cell Adhesion Substrates: Possibility of Applications for Mechanobiology Research

“…In the case of signal transduction of mechanical cues from the ECM, conformational changes in proteins are occasionally important. 10,43 When integrins bind to the ECM proteins, integrin conformation dynamically changes and these changes activate downstream intracellular signals. 10 Therefore, using substrate-immobilized antibodies against integrins might possibly omit the signals activated by conformational changes.…”

Quarterly intrinsic disorder digest (April–May–June, 2014)

“…They highlight several proteins, such as focal adhesion kinase (FAK) and vinculin, where the IDPRs present in these proteins modulate conformation thereby modulating cellmatrix adhesion. 46 Heparin is a glycosaminoglycan component of the extracellular matrix which interacts with many proteins and growth factors at the cell surface and in the extracellular matrix. Peysselon et al investigated the relationship between the affinity and kinetics of heparin-protein interactions and the amount of intrinsic disorder in heparin binding proteins.…”

For whom the cells pull: Hydrogel and micropost devices for measuring traction forces

“…Therefore, the efficiency of RGD-functionalized surfaces for cell adhesion depends on the physical chemistry of the macromolecules that harbor RGD and connect this tripeptide to surfaces. In general, the conformation of ECM proteins plays a strong role in cell-ECM binding by making certain areas accessible to cell binding regions [133]. …”