Jan Rozman

Abstract:

Tissue homeostasis, the biological process of maintaining a steady state in tissue via control of cell proliferation and death, is essential for the development, growth, maintenance, and proper function of living organisms. Disruptions to this process can lead to serious diseases and even death. In this study, we use the vertex model for the cell-level description of tissue mechanics to investigate the impact of the tissue environment and local mechanical properties of cells on homeostasis in confined epithelial tissues. We find a dynamic steady state, where the balance between cell divisions and removals sustains homeostasis, and characterise the homeostatic state in terms of cell count, tissue area, homeostatic pressure, and the cells’ neighbour count distribution. This work, therefore, sheds light on the mechanisms underlying tissue homeostasis and highlights the importance of mechanics in its control.

Abstract:

Complex tissue flows in epithelia are driven by intra- and inter-cellular processes that generate, maintain, and coordinate mechanical forces. There has been growing evidence that cell shape anisotropy, manifested as nematic order, plays an important role in this process. Here we extend an active nematic vertex model by replacing substrate friction with internal viscous dissipation, dominant in epithelia not supported by a substrate or the extracellular matrix, which are found in many early-stage embryos. When coupled to cell shape anisotropy, the internal viscous dissipation allows for long-range velocity correlations and thus enables the spontaneous emergence of flows with a large degree of spatiotemporal organisation. We demonstrate sustained flow in epithelial sheets confined to a channel, providing a link between the cell-level vertex model of tissue dynamics and continuum active nematics, whose behaviour in a channel is theoretically understood and experimentally realisable. Our findings also show a simple mechanism that could account for collective cell migration correlated over distances large compared to the cell size, as observed during morphogenesis.

Abstract:

We study a mixture of extensile and contractile cells using a vertex model extended to include active nematic stresses. The two cell populations phase separate over time. While phase separation strengthens monotonically with an increasing magnitude of contractile activity, the dependence on extensile activity is nonmonotonic, so that sufficiently high values reduce the extent of sorting. We interpret this by showing that extensile activity renders the system motile, enabling cells to undergo neighbor exchanges. Contractile cells that come into contact as a result are then more likely to stay connected due to an effective attraction arising from contractile activity.