Cellular heterogeneity is a phenomenon in which cell populations are composed of subpopulations that vary in their behavior. Heterogeneity is particularly pronounced in cancer cells and can affect the efficacy of oncological therapies. Previous studies have considered heterogeneity dynamics to be indicative of evolutionary changes within subpopulations; however, these studies do not consider the short-time morphological plasticity of cells. Physical properties of the microenvironment elasticity have also been poorly investigated within the context of cellular heterogeneity, despite its role in determining cellular behavior. This article demonstrates that cellular heterogeneity can be highly dynamic and dependent on the micromechanical properties of the substrate. During observation, migrating Walker carcinosarcoma WC256 cells were observed to belong to different subpopulations, in which their morphologies and migration strategies differed. Furthermore, the application of an elastic substrate (E = 40 kPa) modified three aspects of cellular heterogeneity: the occurrence of subpopulations, the occurrence of transitions between subpopulations, and cellular migration and morphology. These findings provide a new perspective in the analysis of cellular heterogeneity, whereby it may not be a static feature of cancer cell populations, instead varying over time. This helps further the understanding of cancer cell behavior, including their phenotype and migration strategy, which may help to improve cancer therapies by extending their suitability to investigate tumor heterogeneity.
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