Pulling in models of cell migration.

Abstract

There are numerous biological scenarios in which populations of cells migrate in crowded environments. Typical examples include wound healing, cancer growth, and embryo development. In these crowded environments cells are able to interact with each other in a variety of ways. These include excluded-volume interactions, adhesion, repulsion, cell signaling, pushing, and pulling. One popular way to understand the behavior of a group of interacting cells is through an agent-based mathematical model. A typical aim of modellers using such representations is to elucidate how the microscopic interactions at the cell-level impact on the macroscopic behavior of the population. At the very least, such models typically incorporate volume-exclusion. The more complex cell-cell interactions listed above have also been incorporated into such models; all apart from cell-cell pulling. In this paper we consider this under-represented cell-cell interaction, in which an active cell is able to pull a nearby neighbor as it moves. We incorporate a variety of potential cell-cell pulling mechanisms into on- and off-lattice agent-based volume exclusion models of cell movement. For each of these agent-based models we derive a continuum partial differential equation which describes the evolution of the cells at a population level. We study the agreement between the agent-based models and the continuum, population-based models and compare and contrast a range of agent-based models (accounting for the different pulling mechanisms) with each other. We find generally good agreement between the agent-based models and the corresponding continuum models that worsens as the agent-based models become more complex. Interestingly, we observe that the partial differential equations that we derive differ significantly, depending on whether they were derived from on- or off-lattice agent-based models of pulling. This hints that it is important to employ the appropriate agent-based model when representing pulling cell-cell interactions.