Collective Cell Motion in an Epithelial Sheet Can Be Quantitatively Described by a Stochastic Interacting Particle Model

Modelling the displacement of thousands of cells that move in a collective way is required for the simulation and the theoretical analysis of various biological processes. Here, we tackle this question in the controlled setting where the motion of Madin-Darby Canine Kidney (MDCK) cells in a confluent epithelium is triggered by the unmasking of free surface. We develop a simple model in which cells are described as point particles with a dynamic based on the two premises that, first, cells move in a stochastic manner and, second, tend to adapt their motion to that of their neighbors. Detailed comparison to experimental data show that the model provides a quantitatively accurate description of cell motion in the epithelium bulk at early times. In addition, inclusion of model “leader” cells with modified characteristics, accounts for the digitated shape of the interface which develops over the subsequent hours, providing that leader cells invade free surface more easily than other cells and coordinate their motion with their followers. The previously-described progression of the epithelium border is reproduced by the model and quantitatively explained. Author Summary: Living organisms, from bacteria to large mammals, move not only as single entities but also in groups. This is true for cells in multicellular organisms. The group or collective motion of cells is an important component of development as well as processes like cancer and wound healing. To better understand this phenomenon, we have recorded the displacement of cells as they move collectively on a substrate and invade free space. The results can be accurately described by modelling the motion of cells as random but with a tendency to move at the same velocity as their neighbors. This allows us to analyze conditions under which the invasion of free space takes place, guided by a few cells that have become different of the others, as observed in the experiments. The developed model should serve as a useful basis for the description of other processes that involve collective cell motion.