Epithelial Tissue Mechanics and Collective Migration

Epithelial tissues form cohesive sheets of cells that line organs and body surfaces, balancing solidity to maintain barriers with fluidity to allow remodelling during development, wound healing and disease progression. Mechanical properties of these sheets emerge from the interplay of cell–cell adhesion, cortical tension and active forces generated by the cytoskeleton. Under certain conditions, a densely packed epithelium behaves like a solid, resisting deformation (‘jammed’ state), whereas under others it flows like a fluid (‘unjammed’ state) to enable coordinated movement of cell cohorts. This collective migration is guided by gradients of biochemical signals and mechanosensitive feedback, and can involve transitions between different orientational orders, from locally sixfold (hexatic) arrangements to nematic alignment across larger scales. Understanding how these material states arise and transition underpins insights into tissue morphogenesis, barrier integrity and invasive pathologies such as cancer metastasis.

Research from Nature Portfolio

Recent studies have revealed how multiscale orientational order within confluent epithelial monolayers depends on cell adhesion and density. At small length scales, hexatic order predominates regardless of adhesion molecule expression or substrate stiffness, while the length scale of transition to nematic order varies with intercellular adhesion strength and packing density. In the developing mouse neuroepithelium, interkinetic nuclear movements driven by the cell cycle generate dynamic stresses that maintain high tissue fluidity early in development, with progressive reduction in proliferation rates leading to a gradual glass-like solidification. Work on primary airway epithelia has clarified that the unjamming transition enabling collective migration is mechanistically distinct from the epithelial-to-mesenchymal transition: junctional integrity and barrier function are preserved while cells elongate and align into migrating packs, driven primarily by enhanced cellular propulsion rather than loss of adhesion.

Epithelial Tissue Mechanics and Collective Migration publication trend

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

Technical terms

Jamming transition: A switch from fluid-like to solid-like behaviour in a densely packed cell collective, marked by arrest of cell rearrangements.

Unjamming transition: The reverse process in which a solid-like cellular layer becomes fluid-like, enabling coordinated cell movement.

Hexatic order: Local sixfold orientational arrangement of cells within a tissue, akin to a two-dimensional liquid crystal phase.

Nematic order: Alignment of cellular long axes over mesoscopic scales, characterised by orientational order without positional order.

Interkinetic nuclear movement: Oscillatory migration of cell nuclei within pseudostratified epithelia, affecting cell shape and tissue fluidity.

References

1. Hexanematic crossover in epithelial monolayers depends on cell adhesion and cell density. Nature Communications (2023).
2. State of Cell Unjamming Correlates with Distant Metastasis in Cancer Patients. Physical Review X (2023).
3. Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo. Advanced Science (2023).
4. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics (2023).
5. Motility-Driven Glass and Jamming Transitions in Biological Tissues. Physical Review X (2016).
6. In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition. Nature Communications (2020).