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Dynamics of living cells in a cytomorphological state space.

ABSTRACT: Cells are nonequilibrium systems that exchange matter and energy with the environment to sustain their metabolic needs. The nonequilibrium nature of this system presents considerable challenges to developing a general theory describing its behavior; however, when studied at appropriate spatiotemporal scales, the behavior of ensembles of nonequilibrium systems can resemble that of a system at equilibrium. Here we apply this principle to a population of cells within a cytomorphological state space and demonstrate that cellular transition dynamics within this space can be described using equilibrium formalisms. We use this framework to map the effective energy landscape underlying the cytomorphological state space of a population of mouse embryonic fibroblasts (MEFs) and identify topographical nonuniformity in this space, indicating nonuniform occupation of cytomorphological states within an isogenic population. The introduction of exogenous apoptotic agents fundamentally altered this energy landscape, inducing formation of additional energy minima that correlated directly with changes in sensitivity to apoptosis induction. An equilibrium framework allows us to describe the behavior of an ensemble of single cells, suggesting that although cells are complex nonequilibrium systems, the application of formalisms derived from equilibrium thermodynamics can provide insight into the basis of nongenetic heterogeneities within cell populations, as well as the relationship between cytomorphological and functional heterogeneity.

SUBMITTER: Chang AY

PROVIDER: S-EPMC6815155 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Dynamics of living cells in a cytomorphological state space.

Chang Amy Y AY Marshall Wallace F WF

Proceedings of the National Academy of Sciences of the United States of America 20191007 43

Cells are nonequilibrium systems that exchange matter and energy with the environment to sustain their metabolic needs. The nonequilibrium nature of this system presents considerable challenges to developing a general theory describing its behavior; however, when studied at appropriate spatiotemporal scales, the behavior of ensembles of nonequilibrium systems can resemble that of a system at equilibrium. Here we apply this principle to a population of cells within a cytomorphological state space ...[more]

PMID: 31591210

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Dataset Information

Dynamics of living cells in a cytomorphological state space.

Publications

Dynamics of living cells in a cytomorphological state space.

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