Cell Adhesion Mechanisms in Extracellular Matrix Interactions

Cells adhere to their surrounding extracellular matrix (ECM) through specialised receptors and molecular assemblies that sense, transmit and respond to mechanical and biochemical cues. Integrins, the predominant heterodimeric receptors, recognise specific peptide motifs within ECM proteins such as fibronectin, collagen and laminin, driving cell attachment, spreading and migration. Ligand binding triggers the recruitment of cytoskeletal and signalling proteins to form focal adhesions, which integrate mechanical tension with intracellular pathways to regulate gene expression, morphology and survival. Non-integrin receptors and proteoglycans, including discoidin domain receptors and syndecans, modulate adhesion dynamics and matrix remodelling. Mechanotransduction, by which forces transmitted via adhesion complexes are converted into biochemical signals, underpins processes from tissue morphogenesis to wound healing. Aberrant adhesion contributes to fibrosis, cancer metastasis and developmental defects. Recent advances have elucidated the dynamic interplay between receptor–ligand affinity, cytoskeletal tension and matrix architecture, highlighting potential therapeutic targets to modulate adhesion in disease and regenerative medicine.

Research from Nature Portfolio

Studies of human skin equivalents under controlled mechanical tension have revealed that tensional homeostasis optimises the organisation of dermal ECM fibres and enhances homeostatic skin function. Application of horizontal tension in vitro aligned collagen and fibronectin networks, promoting cell–matrix contacts through activation of mechano-sensitive effectors such as ROCK and MRTF-A. These findings demonstrate that balanced traction forces not only maintain structural integrity but also drive matrix remodelling and cell differentiation, offering a refined model to study tissue physiology and design biomimetic platforms for drug testing.

Cell Adhesion Mechanisms in Extracellular Matrix Interactions publication trend

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

Technical terms

Integrin: A transmembrane heterodimeric receptor that binds ECM ligands and links to the cytoskeleton to mediate adhesion and signal transduction.

Extracellular matrix (ECM): A complex network of proteins and polysaccharides that provides structural support and biochemical signals to surrounding cells.

Mechanotransduction: The process by which cells convert mechanical stimuli from their environment into biochemical signals.

Focal adhesion: A multi-protein complex that forms at sites of integrin-ECM engagement and connects the extracellular ligand to the actin cytoskeleton.

Arg-Gly-Asp (RGD) motif: A specific tripeptide sequence found in several ECM proteins that is recognised by many integrin receptors.

References

1. Tissue-scale tensional homeostasis in skin regulates structure and physiological function. Communications Biology (2020).
2. Regulation of the fibronectin receptor affinity by divalent cations.. Journal of Biological Chemistry (1988).
3. Regulation of Cell Adhesion Receptors by Transforming Growth Factor-β Concomitant regulation of integrins that share a common β1 subunit. Journal of Biological Chemistry (1989).