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Cell morphology and mechanosensing can be decoupled in fibrous microenvironments and identified using artificial neural networks
Journal article   Open access   Peer reviewed

Cell morphology and mechanosensing can be decoupled in fibrous microenvironments and identified using artificial neural networks

Edward D. Bonnevie, Beth G. Ashinsky, Bassil Dekky, Susan W. Volk, Harvey E. Smith, Robert L. Mauck and Alan T Murray
Scientific reports, v 11(Mar (E-published)), pp 5950-5950
15 Mar 2021
PMID: 33723274
url
https://www.nature.com/articles/s41598-021-85276-5.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1038/s41598-021-85276-5View
Published, Version of Record (VoR) Open

Abstract

Cellular imaging Mechanotransduction
Cells interpret cues from and interact with fibrous microenvironments through the body based on the mechanics and organization of these environments and the phenotypic state of the cell. This in turn regulates mechanoactive pathways, such as the localization of mechanosensitive factors. Here, we leverage the microscale heterogeneity inherent to engineered fiber microenvironments to produce a large morphologic data set, across multiple cells types, while simultaneously measuring mechanobiological response (YAP/TAZ nuclear localization) at the single cell level. This dataset describing a large dynamic range of cell morphologies and responses was coupled with a machine learning approach to predict the mechanobiological state of individual cells from multiple lineages. We also noted that certain cells (e.g., invasive cancer cells) or biochemical perturbations (e.g., modulating contractility) can limit the predictability of cells in a universal context. Leveraging this finding, we developed further models that incorporate biochemical cues for single cell prediction or identify individual cells that do not follow the established rules. The models developed here provide a tool for connecting cell morphology and signaling, incorporating biochemical cues in predictive models, and identifying aberrant cell behavior at the single cell level.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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