Pulling in models of cell migration

TL;DR

This paper investigates how cell-cell pulling interactions influence cell migration models by incorporating pulling mechanisms into agent-based models and deriving corresponding continuum equations, highlighting differences between on- and off-lattice approaches.

Contribution

It introduces novel pulling mechanisms into agent-based models of cell migration and derives continuum PDEs, comparing their behaviors and emphasizing the importance of model choice.

Findings

Good agreement between ABMs and PDEs, decreasing with complexity.

Derived PDEs differ significantly between on- and off-lattice models.

Model choice impacts the representation of pulling interactions.

Abstract

There are numerous 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 signalling, pushing and pulling. One popular way to understand the behaviour of a group of interacting cells is through an agent-based model (ABM). A typical aim of modellers using such represtations is to elucidate how the microscopic interactions at the cell-level impact on the macroscopic behaviour of the population. The 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 neighbour 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 ABMs and the continuum, population-based models, and compare and contrast a range of ABMs (accounting for the different pulling mechanisms) with each other. We find generally good agreement between the ABMs 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 ABMs of pulling. This hints that it is important employ the appropriate ABM when representing pulling cell-cell interactions.