Physics of tissue fluidity and collective cell motion in epithelia

Collective cell migration is essential in many fundamental biological processes. During morphogenesis, cells display highly coordinated shape changes, rearrangements, and motion. During wound healing, cells must coordinate their migration to close gaps in epithelial tissues to prevent infection. The efficiency of these processes is determined by the fluidity of the tissue --- the ability for cells to rearrange and remodel, which in turn is governed by the mechanics of both the cells and their environment. In this thesis, I use computational methods to investigate the origin of tissue fluidity, and its role on collective cell motion. In Part I, I investigate how tissue fluidity governs collective cell motion during wound healing. We find that the ability for cells to rearrange, preventing jamming, is essential for closure. Despite contractile tension around the gap driving closure, reducing tension in the cells increases tissue fluidity and healing rates. In Part II, I study how cells optimise their active behaviour, either contraction or crawling, to regulate tissue fluidity for rapid motion. In wound healing, we find that a balance of the two modes is most efficient over a wide range of cell, substrate, and tissue properties. In Part III, I study how tissue fluidity regulates force transmission in cell colonies. For stiff cells, the tissue acts like a giant single-cell, with traction forces distributed around the colony periphery, but as tissue fluidity increases, forces localise to the interior of the colony. Tissue fluidity requires that cells are able to rearrange and change shape, which in turn is regulated by adaptive viscoelastic properties of the junctions. Thus, in Part IV, I develop a new theory for how cell-cell junctions remodel under stress; strain above a threshold triggers tension remodelling and irreversible length changes. This enables tissue shape change and homeostasis that is robust to fluctuations in stress. Overall, this work demonstrates the important role of single cell mechanics and tissue fluidity on regulating collective cell behaviours.