Distinguishing between mechanisms of cell aggregation using pair-correlation functions

Agnew, D.J.G., Green, J.E.F., Brown, T.M., Simpson, M.J., & Binder, B.J. (2014) Distinguishing between mechanisms of cell aggregation using pair-correlation functions. Journal of Theoretical Biology, 352, pp. 16-23.

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Many cell types form clumps or aggregates when cultured in vitro through a variety of mechanisms including rapid cell proliferation, chemotaxis, or direct cell-to-cell contact. In this paper we develop an agent-based model to explore the formation of aggregates in cultures where cells are initially distributed uniformly, at random, on a two-dimensional substrate. Our model includes unbiased random cell motion, together with two mechanisms which can produce cell aggregates: (i) rapid cell proliferation, and (ii) a biased cell motility mechanism where cells can sense other cells within a finite range, and will tend to move towards areas with higher numbers of cells. We then introduce a pair-correlation function which allows us to quantify aspects of the spatial patterns produced by our agent-based model. In particular, these pair-correlation functions are able to detect differences between domains populated uniformly at random (i.e. at the exclusion complete spatial randomness (ECSR) state) and those where the proliferation and biased motion rules have been employed - even when such differences are not obvious to the naked eye. The pair-correlation function can also detect the emergence of a characteristic inter-aggregate distance which occurs when the biased motion mechanism is dominant, and is not observed when cell proliferation is the main mechanism of aggregate formation. This suggests that applying the pair-correlation function to experimental images of cell aggregates may provide information about the mechanism associated with observed aggregates. As a proof of concept, we perform such analysis for images of cancer cell aggregates, which are known to be associated with rapid proliferation. The results of our analysis are consistent with the predictions of the proliferation-based simulations, which supports the potential usefulness of pair correlation functions for providing insight into the mechanisms of aggregate formation.

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ID Code: 67857
Item Type: Journal Article
Refereed: Yes
Keywords: cell aggregates, spatial patterns, agent-based model, cell-based experiments, pair-correlation functions, cell proliferation, chemotaxis, cell-cell interaction
DOI: 10.1016/j.jtbi.2014.02.033
ISSN: 0022-5193
Subjects: Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000) > APPLIED MATHEMATICS (010200)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Mathematical Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2014 Elsevier
Copyright Statement: This is the author’s version of a work that was accepted for publication in Journal of Theoretical Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Theoretical Biology, [VOL 352, (2014)] DOI: 10.1016/j.jtbi.2014.02.033
Deposited On: 27 Feb 2014 01:04
Last Modified: 06 Aug 2015 01:52

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