Cell division and death inhibit glassy behaviour of confluent tissues

Abstract

We investigate the effects of cell division and apopotosis on collective dynamics in two-dimensional epithelial tissues. Our model includes three key ingredients observed across many epithelia, namely cell-cell adhesion, cell death and a cell division process that depends on the surrounding environment. We show a rich non-equilibrium phase diagram depending on the ratio of cell death to cell division and on the adhesion strength. For large apopotosis rates, cells die out and the tissue disintegrates. As the death rate decreases, however, we show, consecutively, the existence of a gas-like phase, a gel-like phase, and a dense confluent (tissue) phase. Most striking is the observation that the tissue is self-melting through its own internal activity, ruling out the existence of any glassy phase.

Cell Growth Rate Dictates the Onset of Glass to Fluidlike Transition and Long Time Superdiffusion in an Evolving Cell Colony

“…for tracer cells (ones that have all the characteristics of cells, except that they are alive throughout the simulations and do not grow or divide) shows no caging effects but grows linearly with time [27], suggestive of normal diffusion. In light of this dramatically different behavior reported in [27], we performed simulations using our model by including 100 randomly placed tracer cells.…”

“…Elsewhere [27], using a two-dimensional model, ΔðtÞ was computed for cells, as well as tracer cells. In that study, using periodic boundary conditions, the choice of birth and death rates was such that in the long time limit homeostasis was always reached where the birth and death of cells were balanced.…”

“…In an attempt to capture collective dynamics in cells, a number of models based on cellular automata [13,14], vertex and Voronoi models [15][16][17][18][19], subcellular element models [20], cell dynamics based on the Potts model [21,22], and the phase field description for collective migration [23,24] have been proposed. Previous works have investigated a number of two-dimensional (2D) models in various contexts [9,16,25], including probing the dynamics in a homeostatic state where cell birth-death processes are balanced [26,27]. Existing three-dimensional (3D) models focus solely on tumor growth kinetics, spatial growth patterns [28,29], or on cell migration at low cellular density on timescales shorter than the cell division time [30][31][32].…”

“…A recent interesting study [26] shows that cell dynamics in a confluent tissue is always fluidized by cell birth and death processes, on timescales comparable to cell division time. A more recent two-dimensional model [27] investigates the glass-to-liquid transition in confluent tissues using simulations. However, both of these instructive models [26,27] focus on the steady-state regime, where the number of tumor cells is kept constant by balancing the birth and death rates.…”

“…A more recent two-dimensional model [27] investigates the glass-to-liquid transition in confluent tissues using simulations. However, both of these instructive models [26,27] focus on the steady-state regime, where the number of tumor cells is kept constant by balancing the birth and death rates. Consequently, they do not address the nonequilibrium dynamics of the evolving tumor in the early stages, which is of great interest in cancer biology [33][34][35].…”