Cellular Mechanics in Epithelial Systems

Epithelial tissues form selective barriers across organs, maintaining homeostasis through coordinated cell adhesion, migration and proliferation. Mechanical properties of cells and their microenvironment govern tissue integrity and function, influencing processes such as morphogenesis, wound healing and tumour invasion. At the cellular level, forces transmitted by the actomyosin cytoskeleton, cell–cell junctions and interactions with the extracellular matrix integrate mechanical cues into biochemical signalling. Mechanotransduction pathways involving transcriptional regulators, ion channels and adhesion complexes enable epithelial cells to sense substrate stiffness, tensile stress and crowding. Alterations in cortical tension, membrane–cortex attachment and cytoskeletal organisation can shift epithelial behaviour between quiescence, collective migration and individual dissemination. Understanding the balance of forces within epithelial monolayers and three-dimensional structures is central to deciphering how tissues adapt to physiological challenges and how mechanical dysregulation contributes to disease.

Research from Nature Portfolio

Recent studies have revealed that differential attachment between the plasma membrane and underlying cortex defines distinct mechanical phenotypes in cancer organoids. In colorectal models, cells expressing stem-cell markers exhibit increased stiffness, enhanced matrix adhesion and greater resistance to confinement, favouring metastatic seeding, whereas more pliant cells adopt a motile phenotype optimal for dissemination. In embryonic tissues, collective cell clusters dynamically soften through mechanosensitive microtubule deacetylation mediated by stretch-activated channels, triggering migration even on compliant substrates; this demonstrates that an optimal ratio of cluster to substrate stiffness is essential for coordinated movement in vivo. Seminal work on epidermal stem cells has established that tension-dependent regulation of YAP/TAZ transcriptional co-activators links matrix rigidity to Notch signalling, thus controlling the balance between self-renewal and differentiation in stratified epithelium.

Cellular Mechanics in Epithelial Systems publication trend

The graph below shows the total number of articles in cellular mechanics in epithelial systems across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial cells: Polarised cells forming continuous sheets that line organ surfaces and cavities.

Extracellular matrix (ECM): A network of proteins and polysaccharides providing structural support and biochemical signals.

Actomyosin contractility: Force generation by interactions between actin filaments and myosin motors within the cell cortex.

Mechanotransduction: Conversion of mechanical stimuli into intracellular biochemical responses.

Contact inhibition: Cessation of cell proliferation upon establishment of mature intercellular junctions.

Organoid: Three-dimensional multicellular structure derived from stem cells that mimics organ architecture.

YAP/TAZ: Transcriptional co-activators regulated by mechanical cues that modulate cell fate decisions.

References

1. Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells. Nature Communications (2024).
2. Cell clusters softening triggers collective cell migration in vivo. Nature Materials (2022).
3. YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate. Nature Communications (2017).
4. Oct4 is a gatekeeper of epithelial identity by regulating cytoskeletal organization in skin keratinocytes. Cell Reports (2024).
5. Mechanically-driven stem cell separation in tissues caused by proliferating daughter cells. SciPost Physics (2024).
6. Continuum Theory of Active Phase Separation in Cellular Aggregates. Physical Review Letters (2021).