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Modeling mechanical inhomogeneities in small populations of proliferating monolayers and spheroids.

Abstract：

:Understanding the mechanical behavior of multicellular monolayers and spheroids is fundamental to tissue culture, organism development, and the early stages of tumor growth. Proliferating cells in monolayers and spheroids experience mechanical forces as they grow and divide and local inhomogeneities in the mechanical microenvironment can cause individual cells within the multicellular system to grow and divide at different rates. This differential growth, combined with cell division and reorganization, leads to residual stress. Multiple different modeling approaches have been taken to understand and predict the residual stresses that arise in growing multicellular systems, particularly tumor spheroids. Here, we show that by using a mechanically robust agent-based model constructed with the peridynamic framework, we gain a better understanding of residual stresses in multicellular systems as they grow from a single cell. In particular, we focus on small populations of cells (1-100 s) where population behavior is highly stochastic and prior investigation has been limited. We compare the average strain energy density of cells in monolayers and spheroids using different growth and division rules and find that, on average, cells in spheroids have a higher strain energy density than cells in monolayers. We also find that cells in the interior of a growing spheroid are, on average, in compression. Finally, we demonstrate the importance of accounting for stochastic fluctuations in the mechanical environment, particularly when the cellular response to mechanical cues is nonlinear. The results presented here serve as a starting point for both further investigation with agent-based models, and for the incorporation of major findings from agent-based models into continuum scale models when explicit representation of individual cells is not computationally feasible.

journal_name

Biomech Model Mechanobiol

journal_title

Biomechanics and modeling in mechanobiology

authors

Lejeune E,Linder C

doi

10.1007/s10237-017-0989-0

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

727-743

issue

eissn

1617-7959

issn

1617-7940

pii

10.1007/s10237-017-0989-0

journal_volume

pub_type

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Modeling mechanical inhomogeneities in small populations of proliferating monolayers and spheroids.