Fluorescent cell cycle labelling in cell biology experiments provides real time information about the location of individual cells, as well as the phase of the cell cycle of individual cells. We develop a stochastic, lattice-based random walk model of a two-dimensional scratch assay where the total population is composed of three distinct subpopulations which we visualise as red, yellow and green subpopulations. Our model mimics FUCCI technology in which cells in the G1 phase of the cell cycle fluoresce red, cells in the early S phase fluoresce yellow, and cells in the S/G2/M phase fluoresce green. The model is an exclusion process so that any potential motility or proliferation event that would place an agent on an occupied lattice site is aborted. Using experimental images and previous experimental measurements we explain how to apply the stochastic model to simulate a scratch assay initialised with a low to moderate density monolayer of human melanoma cell line. We obtain additional mathematical insight by deriving an approximate partial differential equation (PDE) description of the stochastic model, leading to a novel system of three coupled nonlinear reaction diffusion equations. Comparing averaged simulation data with the solution of the continuum limit model confirms that the PDE description is accurate for biologically-relevant parameter combinations.
In this study, we couple intracellular signalling and cell-based mechanical properties to develop a novel free boundary mechanobiological model of epithelial tissue dynamics. Mechanobiological coupling is introduced at the cell level in a discrete modelling framework, and new reaction–diffusion equations are derived to describe tissue-level outcomes. The free boundary evolves as a result of the underlying biological mechanisms included in the discrete model. To demonstrate the accuracy of the continuum model, we compare numerical solutions of the discrete and continuum models for two different signalling pathways. First, we study the Rac–Rho pathway where cell- and tissue-level mechanics are directly related to intracellular signalling. Second, we study an activator–inhibitor system which gives rise to spatial and temporal patterning related to Turing patterns. In all cases, the continuum model and free boundary condition accurately reflect the cell-level processes included in the discrete model.
The detachment of cells from the boundary of an epithelial tissue and the subsequent invasion of these cells into surrounding tissues is important for cancer development and wound healing, and is strongly associated with the epithelial-mesenchymal transition (EMT). Chemical signals, such as TGF-β, produced by surrounding tissue can be uptaken by cells and induce EMT. In this work, we present a novel cell-based discrete mathematical model of mechanical cellular relaxation, cell proliferation, and cell detachment driven by chemically-dependent EMT in an epithelial tissue. A continuum description of the model is then derived in the form of a novel nonlinear free boundary problem. Using the discrete and continuum models we explore how the coupling of chemical transport and mechanical interactions influences EMT, and postulate how this could be used to help control EMT in pathological situations.
The detachment of cells from the boundary of an epithelial tissue and the subsequent invasion of these cells into surrounding tissues is important for cancer development and wound healing, and is strongly associated with the epithelial-mesenchymal transition (EMT). Chemical signals, such as TGF-β, produced by surrounding tissue can be up-taken by cells and induce EMT. In this work, we present a novel cell-based discrete mathematical model of mechanical cellular relaxation, cell proliferation, and cell detachment driven by chemically-dependent EMT in an epithelial tissue. A continuum description of the model is then derived in the form of a novel nonlinear free boundary problem. Using the discrete and continuum models we explore how the coupling of chemical transport and mechanical interactions influences EMT, and postulate how this could be used to help control EMT in pathological situations.
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