Abstract
In this work, we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell–cell interactions. This is important as cell–cell interactions, such as adhesion and repulsion, have been shown to play a role in cell migration. Initially, we demonstrate with a model of an unrealistic experiment that we are able to identify model parameters that describe agent motility and adhesion, given we choose appropriate summary statistics for our model data. Following this, we replace our model of an unrealistic experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, our model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental replicates. The results presented in this work, therefore, describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell–cell adhesion or repulsion are known to play a significant role.
Highlights
Cell–cell interactions are known to play an important role in several cell migration processes
We have shown previously that different cell–cell interactions have different effects on the agent density profile.[36]
Summarises the displacement of agents into the ‘wound’. This displacement is affected by the adhesion of iag1⁄4enN1 tPs aNk1⁄4n1ditktihÀeiirtkfmÁ otility rate
Summary
Cell–cell interactions are known to play an important role in several cell migration processes. Repulsive interactions mediated via ephrins on the surface of neural crest stem cells are known to coordinate the early stages of melanoblast migration away from the neural tube.[2] More fundamentally, it is hypothesised that the emergence of cell–cell interactions over one billion years ago helped establish the necessary conditions for multicellular organisms.[3]. We use an ABM to simulate a wound-healing assay (Wound-healing assays are often referred to as scratch assays.), an experiment commonly used for studying cell motility.[9,10,11,12,13,14,15] Other modelling approaches apart from ABMs have been employed to study wound-healing. We employ an ABM in this work because they provide an intuitive representation of cells, and allow for complex behaviours representing biological processes, such as cell–cell interactions and volume exclusion, to be assigned to agents in the ABM
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