Integrin-Mediated Cell Adhesion Dynamics in Extracellular Matrix Interactions

Integrins are heterodimeric receptors that anchor cells to the extracellular matrix (ECM) and coordinate bidirectional signalling to regulate adhesion, migration, proliferation and differentiation. Through the assembly of multiprotein adhesion complexes they transmit mechanical forces across the plasma membrane, a process central to mechanotransduction and tissue homeostasis. Adhesion sites dynamically recruit cytoskeletal and signalling proteins to calibrate binding strength and specificity, allowing cells to sense matrix rigidity, topography and composition. Integrin engagement with ECM ligands such as fibronectin, collagen and laminin triggers conformational changes that promote clustering into focal adhesions and specialised adhesion modalities adapted to distinct microenvironments. Dysregulation of these processes contributes to cancer metastasis, fibrosis, immune responses and developmental disorders. Advances in imaging and proteomic profiling have begun to unravel the spatiotemporal hierarchy of integrin-associated complexes, revealing mechanisms by which curvature, matrix composition and intracellular regulators tune adhesion dynamics and downstream gene expression.

Research from Nature Portfolio

Recent studies have uncovered novel modes of integrin-mediated adhesion and their influence on intracellular organisation. One investigation identified a curvature-sensing adhesion pathway in which membrane topography imposed by three-dimensional ECM fibres promotes the formation of “curved adhesions” mediated by αvβ5 integrin and a curvature-sensing scaffold protein. These sites differ molecularly from classical focal adhesions and are essential for cell anchorage and migration in soft, fibrous matrices. In parallel, systems-level analysis of the integrin adhesome in carcinoma cells revealed that an actin regulatory protein within adhesion complexes also localises to the nuclear envelope, where it modulates nuclear architecture, chromatin positioning and transcriptional outputs. This work highlights a direct link between integrin adhesion complexes and gene regulation via nucleo-cytoskeletal coupling.

Integrin-Mediated Cell Adhesion Dynamics in Extracellular Matrix Interactions publication trend

The graph below shows the total number of articles in integrin-mediated cell adhesion dynamics in extracellular matrix interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Integrin: Heterodimeric transmembrane receptor comprising α and β subunits that binds ECM ligands and transduces signals.

Extracellular matrix (ECM): Three-dimensional network of proteins and polysaccharides that provides structural support and biochemical cues to cells.

Focal adhesion: Multiprotein assembly linking clustered integrins to the actin cytoskeleton and coordinating mechanical and chemical signalling.

Curved adhesion: Membrane-curvature-dependent integrin adhesion complex distinct from focal adhesions, important for 3D matrix anchorage.

Mechanotransduction: Cellular process by which mechanical forces are converted into biochemical signals via adhesion molecules and cytoskeletal linkages.

Actin cytoskeleton: Network of filamentous actin that provides structural support, enables force transmission and organises adhesion complexes.

References

1. Curved adhesions mediate cell attachment to soft matrix fibres in three dimensions. Nature Cell Biology (2023).
2. Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression. Nature Communications (2023).
3. Protein kinase B (AKT) upregulation and Thy-1-αvβ3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis. Journal of Neuroinflammation (2023).
4. Integrins as a bridge between bacteria and cells: key targets for therapeutic wound healing. Burns & Trauma (2024).
5. The Collagen-binding A-domains of Integrins α1β1 and α2β1Recognize the Same Specific Amino Acid Sequence, GFOGER, in Native (Triple-helical) Collagens*. Journal of Biological Chemistry (2000).