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DLITE Uses Cell-Cell Interface Movement to Better Infer Cell-Cell Tensions.

ABSTRACT: Cell shapes and connectivities evolve over time as the colony changes shape or embryos develop. Shapes of intercellular interfaces are closely coupled with the forces resulting from actomyosin interactions, membrane tension, or cell-cell adhesions. Although it is possible to computationally infer cell-cell forces from a mechanical model of collective cell behavior, doing so for temporally evolving forces in a manner robust to digitization difficulties is challenging. Here, we introduce a method for dynamic local intercellular tension estimation (DLITE) that infers such evolution in temporal force with less sensitivity to digitization ambiguities or errors. This method builds upon previous work on single time points (cellular force-inference toolkit). We validate our method using synthetic geometries. DLITE's inferred cell colony tension evolutions correlate better with ground truth for these synthetic geometries as compared to tension values inferred from methods that consider each time point in isolation. We introduce cell connectivity errors, angle estimate errors, connection mislocalization, and connection topological changes to synthetic data and show that DLITE has reduced sensitivity to these conditions. Finally, we apply DLITE to time series of human-induced pluripotent stem cell colonies with endogenously expressed GFP-tagged zonulae occludentes-1. We show that DLITE offers improved stability in the inference of cell-cell tensions and supports a correlation between the dynamics of cell-cell forces and colony rearrangement.

SUBMITTER: Vasan R

PROVIDER: S-EPMC6838938 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIdentifying the behavioral state for wild animals that can't be directly observed is of growing interest to the ecological community. Advances in telemetry technology and statistical methodologies allow researchers to use space-use and movement metrics to infer the underlying, latent, behavioral state of an animal without direct observations. For example, researchers studying ungulate ecology have started using these methods to quantify behaviors related to mating strategies. However, little work has been done to determine if assumed behaviors inferred from movement and space-use patterns correspond to actual behaviors of individuals.MethodsUsing a dataset with male and female white-tailed deer location data, we evaluated the ability of these two methods to correctly identify male-female interaction events (MFIEs). We identified MFIEs using the proximity of their locations in space as indicators of when mating could have occurred. We then tested the ability of utilization distributions (UDs) and hidden Markov models (HMMs) rendered with single sex location data to identify these events.ResultsFor white-tailed deer, male and female space-use and movement behavior did not vary consistently when with a potential mate. There was no evidence that a probability contour threshold based on UD volume applied to an individual's UD could be used to identify MFIEs. Additionally, HMMs were unable to identify MFIEs, as single MFIEs were often split across multiple states and the primary state of each MFIE was not consistent across events.ConclusionsCaution is warranted when interpreting behavioral insights rendered from statistical models applied to location data, particularly when there is no form of validation data. For these models to detect latent behaviors, the individual needs to exhibit a consistently different type of space-use and movement when engaged in the behavior. Unvalidated assumptions about that relationship may lead to incorrect inference about mating strategies or other behaviors.

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DLITE Uses Cell-Cell Interface Movement to Better Infer Cell-Cell Tensions.

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