Understanding the relationship between cell death and tissue shrinkage via a stochastic agent-based model
Authored by E Lejeune
Date Published: 2018
DOI: 10.1016/j.jbiomech.2018.03.019
Sponsors:
United States National Science Foundation (NSF)
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Abstract
Cell death, a process which can occur both naturally and in response to
insult, is both a complex and diverse phenomenon. Under some
circumstances, dying cells actively contract and cause their neighbors
to rearrange and maintain tissue integrity. Under other circumstances,
dying cells leave behind gaps, which results in tissue separation. A
better understanding of how the cellular scale features of cell death
manifest on the population scale has implications ranging from
morphogenesis to tumor response to treatment. However, the mechanistic
relationship between cell death and population scale shrinkage is not
well understood, and computational methods for studying these
relationships are not well established. Here we propose a mechanically
robust agent-based cell model designed to capture the implications of
cell death on the population scale. In our agent-based model,
algorithmic rules applied on the cellular level emerge on the population
scale where their effects are quantified. To better quantify model
uncertainty and parameter interactions, we implement a recently
developed technique for conducting a variance-based sensitivity analysis
on the stochastic model. From this analysis and subsequent
investigation, we find that cellular scale shrinkage has the largest
influence of all model parameters tested, and that by adjusting cellular
scale shrinkage population shrinkage varies widely even across
simulations which contain the same fraction of dying cells. We
anticipate that the methods and results presented here are a starting
point for significant future investigation toward quantifying the
implications of different mechanisms of cell death on population and
tissue scale behavior. (C) 2018 Elsevier Ltd. All rights reserved.
Tags
Agent-based model
Dynamics
Sensitivity Analysis
apoptosis
multi-scale model
Tumor-growth
Sensitivity-analysis
Indexes
Forces
Spheroids
Cell death
Tissue shrinkage
Systems-biology