Mechanical Dynamics of Epithelial Cell Homeostasis

Epithelial tissues maintain a continuous barrier by balancing cell proliferation, differentiation and removal. Mechanical forces arising within and between cells govern this balance, shaping cell packing, tension distribution and tissue morphology. Cells sense crowding through mechanotransduction pathways that translate membrane and cytoskeletal deformations into biochemical signals, adjusting growth or triggering extrusion of surplus or damaged cells. Intercellular adhesion complexes and actomyosin networks cooperate to generate contractile forces along cell–cell interfaces, while attachments to extracellular matrix provide resistance and spatial cues. The apical and basal surfaces of epithelia exhibit organised cytoskeletal architectures that direct force vectors during processes such as wound closure, morphogenetic folding and pathogen response. Mechanical cell competition eliminates weaker or aberrant cells, thus preserving tissue integrity and preventing early tumour formation. Conversely, dysregulation of force transmission can lead to barrier defects, invasive behaviour or impaired regeneration. Understanding these dynamics has broad implications for regenerative medicine, cancer prevention and the design of biomimetic materials that emulate epithelial mechanics.

Research from Nature Portfolio

Recent studies have shown that differences in force transmission capabilities between neighbouring epithelial cells drive mechanical cell competition, with stronger intercellular adhesion conferring resistance to elimination and preserving tissue boundaries. Direct measurements of stress fluctuations at competing interfaces reveal that cells endowed with enhanced adhesion exert upward forces on less adhesive neighbours, leading to their extrusion. Another investigation demonstrates that apoptotic cell extrusion is mediated by a dual‐mode actin network in surrounding cells. Early lamellipodia protrusions at the basal surface seal the extrusion site and orient the supracellular actomyosin cable, while discontinuous contractile fibres at the apical surface generate the primary driving force. A theoretical framework integrating cell–cell and cell–substrate adhesions explains why this combined mechanism accelerates removal of dying cells compared with a single contractile ring.

Mechanical Dynamics of Epithelial Cell Homeostasis publication trend

The graph below shows the total number of articles in mechanical dynamics of epithelial cell homeostasis across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial homeostasis: The dynamic equilibrium of cell proliferation, differentiation and removal that maintains epithelial barrier function.

Mechanotransduction: The process by which cells convert mechanical stimuli into biochemical signals to regulate behaviour.

Actomyosin purse‐string: A contractile ring of actin filaments and myosin motors formed by neighbouring cells to drive cell extrusion.

Cell extrusion: The active removal of unwanted or dying cells from an epithelial sheet to preserve tissue integrity.

ERK activation waves: Spatiotemporal propagations of kinase activity that coordinate cell responses over multicellular distances.

References

1. Force transmission is a master regulator of mechanical cell competition. Nature Materials (2025).
2. Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion. Nature Communications (2021).
3. ERK activation waves coordinate mechanical cell competition leading to collective elimination via extrusion of bacterially infected cells. Cell Reports (2025).
4. Reduction of endocytosis and EGFR signaling is associated with the switch from isolated to clustered apoptosis during epithelial tissue remodeling in Drosophila. PLOS Biology (2024).
5. Calcium Wave Promotes Cell Extrusion. Current Biology (2020).