Cadherin-Mediated Cell Adhesion in Tissue Morphogenesis

Cadherins are a family of calcium-dependent transmembrane proteins that mediate homophilic adhesion between neighbouring cells, underpinning the assembly and maintenance of tissues throughout development and homeostasis. Through trans interactions that bridge apposed cell membranes and cis interactions that cluster cadherins laterally, adherens junctions and desmosomes form mechanically robust contacts linked to the actin and intermediate filament cytoskeletons via catenins. These contacts not only provide tensile strength but also serve as hubs for intracellular signalling and mechanotransduction, guiding processes such as embryonic germ layer segregation, organ shaping and collective cell migration during wound repair. Dynamic regulation of cadherin adhesion—via changes in expression, post-translational modification or mechanical cues—ensures that tissues can remodel while preserving integrity. Dysregulation of cadherin function contributes to developmental defects, impaired barrier formation and cancer invasion, highlighting the global significance of understanding the molecular and biophysical principles governing cadherin-mediated adhesion in tissue morphogenesis.

Research from Nature Portfolio

Recent studies have introduced optogenetic control of E-cadherin, engineering a light-sensitive variant that allows reversible modulation of calcium-dependent adhesion with blue light. This tool permits precise spatiotemporal investigation of cell-cell contacts, collective migration modes and cytoskeletal organisation in both two- and three-dimensional cultures. Complementary work has demonstrated that weak, multivalent hydrophobic interactions alone can drive the lateral clustering of cadherin-23 on membranes without requiring specific cis-dimer bonds. Such clustering accelerates cell-cell adhesion kinetics and reinforces junction strength, suggesting a role for phase-separation principles in rapid tissue assembly. In parallel, biochemical and computational analyses of single nucleotide polymorphisms in a non-classical cadherin have shown that minor amino acid substitutions can weaken homodimerisation, reduce cell aggregation and promote metastatic dissemination in a colorectal cancer model, thereby linking cadherin adhesion energy to disease progression.

Cadherin-Mediated Cell Adhesion in Tissue Morphogenesis publication trend

The graph below shows the total number of articles in cadherin-mediated cell adhesion in tissue morphogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Cadherin: A calcium-dependent transmembrane protein that mediates homophilic adhesion between cells.

Homophilic adhesion: Binding between identical cadherin molecules on adjacent cell surfaces.

Cis interaction: Lateral association of cadherins within the same cell membrane.

Trans interaction: Adhesive binding of cadherins across the intercellular space.

Homodimerisation: Association of two identical cadherin extracellular domains to form a functional adhesive unit.

Optogenetics: Use of light-sensitive proteins to control cellular processes with high spatiotemporal precision.

Desmosome: A specialised intercellular junction rich in cadherins that confers strong mechanical coupling between cells.

References

1. Reversible photoregulation of cell-cell adhesions with opto-E-cadherin. Nature Communications (2023).
2. Transient interactions drive the lateral clustering of cadherin-23 on membrane. Communications Biology (2023).
3. Arrhythmogenic cardiomyopathy-related cadherin variants affect desmosomal binding kinetics. Journal of Molecular and Cellular Cardiology (2024).
4. Molecular mechanism underlying the increased risk of colorectal cancer metastasis caused by single nucleotide polymorphisms in LI-cadherin gene. Scientific Reports (2023).
5. Mechano-Transduction: From Molecules to Tissues. PLOS Biology (2014).
6. Cadherin clusters stabilized by a combination of specific and nonspecific cis-interactions. eLife (2020).