Connecting gene expression to cellular movement: A transport model for cell migration.

The adhesion properties and the mobility of biological cells play key roles in the propagation of cancer. These properties are expected to depend on intracellular processes and on the concentrations of chemicals inside the cell. While most existing reaction-diffusion models for cell migration consider that cell mobility and proliferation rate are constant or depend on an external diffusing species, they do not include the gene expression dynamics taking place in moving cells that affect cellular transport. In this work, we propose a multiscale model where mobility and proliferation depend explicitly on the cell's internal state. We focus more specifically on the case of cellular mobility in epithelial tissues. Wound-healing experiments have demonstrated that the loss of a key protein, E-cadherin, results in a significant increase in both mobility and invasiveness of epithelial cells, with dramatic consequences on cancer progression. We can reproduce the results of these experiments under various genetic conditions with a single set of parameters.

Modelling the propagation of a dynamical signature in gene expression mediated by the transport of extracellular microRNAs.

Extracellular microRNAs (miRNAs) carried by exosomes can play a key role in cell-to-cell communication. Deregulation of miRNA expression and exosome secretion have been related to pathological conditions such as cancer. While it is known that circulating miRNAs can alter gene expression in recipient cells, it remains unclear how significant the dynamical impact of these extracellular miRNAs is. To shed light on this issue, we propose a model for the spatio-temporal evolution of the protein expression in a cell tissue altered by abnormal miRNA expression in a donor cell. This results in a nonhomogeneous cellular response in the tissue, which we quantify by studying the range of action of the donor cell on the surrounding cells. Key model parameters that control the range of action are identified. Based on a model for a heterogeneous cell population, we show that the dynamics of gene expression in the tissue is robust to random changes of the parameter values. Furthermore, we study the propagation of gene expression oscillations in a tissue induced by extracellular miRNAs. In the donor cell, the miRNA inhibits its own transcription which can give rise to local oscillations in gene expression. The resulting oscillations of the concentration of extracellular miRNA induce oscillations of the protein concentration in recipient cells. We analyse the nonmonotonic spatial evolution of the oscillation amplitude of the protein concentration in the tissue which may have implications for the propagation of oscillations in biological rhythms such as the circadian clock.