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Collective cell migration over long time scales reveals distinct phenotypes.

ABSTRACT: Introduction:Migratory phenotypes of metastasizing tumor cells include single and collective cell migration. While migration of tumor cells is generally less cooperative than that of normal epithelial cells, our understanding of precisely how they differ in long time behavior is incomplete. Objectives:We measure in a model system how cancer progression affects collective migration on long time scales, and determine how perturbation of cell-cell adhesions, specifically reduced E-cadherin expression, affects the collective migration phenotype. Methods:Time lapse imaging of cellular sheets and particle image velocimetry (PIV) are used to quantitatively study the dynamics of cell motion over ten hours. Long time dynamics are measured via finite time Lyapunov exponents (FTLE) and changes in FTLE with time. Results:We find that non-malignant MCF10A cells are distinguished from malignant MCF10CA1a cells by both their short time (minutes) and long time (hours) dynamics. In addition, short time dynamics distinguish non-malignant E-cadherin knockdown cells from the control, but long time dynamics and increasing spatial correlations remain unchanged. Discussion:Epithelial sheet collective behavior includes long time dynamics that cannot be captured by metrics that assess cooperativity based on short time dynamics, such as instantaneous speed or directionality. The use of metrics incorporating migration data over hours instead of minutes allows us to more precisely describe how E-cadherin, a clinically relevant adhesion molecule, affects collective migration. We predict that the long time scale metrics described here will be more robust and predictive of malignant behavior than analysis of instantaneous velocity fields alone.

SUBMITTER: Lee RM

PROVIDER: S-EPMC5895103 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Collective cell migration over long time scales reveals distinct phenotypes.

Lee R M RM Stuelten C H CH Parent C A CA Losert W W

Convergent science physical oncology 20160519 2

<h4>Introduction</h4>Migratory phenotypes of metastasizing tumor cells include single and collective cell migration. While migration of tumor cells is generally less cooperative than that of normal epithelial cells, our understanding of precisely how they differ in long time behavior is incomplete.<h4>Objectives</h4>We measure in a model system how cancer progression affects collective migration on long time scales, and determine how perturbation of cell-cell adhesions, specifically reduced E-ca ...[more]

PMID: 29657838

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Project description:BackgroundTime-lapse imaging has proven highly valuable for studying development, yielding data of much finer resolution than traditional "still-shot" studies and allowing direct examination of tissue and cell dynamics. A major challenge for time-lapse imaging of animals is keeping specimens immobile yet healthy for extended periods of time. Although this is often feasible for embryos, the difficulty of immobilizing typically motile juvenile and adult stages remains a persistent obstacle to time-lapse imaging of post-embryonic development.ResultsHere we describe a new method for long-duration time-lapse imaging of adults of the small freshwater annelid Pristina leidyi and use this method to investigate its regenerative processes. Specimens are immobilized with tetrodotoxin, resulting in irreversible paralysis yet apparently normal regeneration, and mounted in agarose surrounded by culture water or halocarbon oil, to prevent dehydration but allowing gas exchange. Using this method, worms can be imaged continuously and at high spatial-temporal resolution for up to 5 days, spanning the entire regeneration process. We performed a fine-scale analysis of regeneration growth rate and characterized cell migration dynamics during early regeneration. Our studies reveal the migration of several putative cell types, including one strongly resembling published descriptions of annelid neoblasts, a cell type suggested to be migratory based on "still-shot" studies and long hypothesized to be linked to regenerative success in annelids.ConclusionsCombining neurotoxin-based paralysis, live mounting techniques and a starvation-tolerant study system has allowed us to obtain the most extensive high-resolution longitudinal recordings of full anterior and posterior regeneration in an invertebrate, and to detect and characterize several cell types undergoing extensive migration during this process. We expect the tetrodotoxin paralysis and time-lapse imaging methods presented here to be broadly useful in studying other animals and of particular value for studying post-embryonic development.

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Collective cell migration over long time scales reveals distinct phenotypes.

Publications

Collective cell migration over long time scales reveals distinct phenotypes.

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