Comparative mapping of crawling-cell morphodynamics in deep learning-based feature space

PLoS Comput Biol. 2021 Aug 12;17(8):e1009237. doi: 10.1371/journal.pcbi.1009237. eCollection 2021 Aug.

Abstract

Navigation of fast migrating cells such as amoeba Dictyostelium and immune cells are tightly associated with their morphologies that range from steady polarized forms that support high directionality to those more complex and variable when making frequent turns. Model simulations are essential for quantitative understanding of these features and their origins, however systematic comparisons with real data are underdeveloped. Here, by employing deep-learning-based feature extraction combined with phase-field modeling framework, we show that a low dimensional feature space for 2D migrating cell morphologies obtained from the shape stereotype of keratocytes, Dictyostelium and neutrophils can be fully mapped by an interlinked signaling network of cell-polarization and protrusion dynamics. Our analysis links the data-driven shape analysis to the underlying causalities by identifying key parameters critical for migratory morphologies both normal and aberrant under genetic and pharmacological perturbations. The results underscore the importance of deciphering self-organizing states and their interplay when characterizing morphological phenotypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cell Polarity / physiology
  • Cell Shape / physiology
  • Cell Surface Extensions / physiology
  • Cells, Cultured
  • Cichlids
  • Computational Biology
  • Computer Simulation
  • Deep Learning*
  • Dictyostelium / cytology
  • Dictyostelium / physiology
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • HL-60 Cells
  • Humans
  • Models, Biological*

Grants and funding

This work was funded by grants from Japan Science and Technology Agency (JST) CREST JPMJCR1923 (to S.S.), Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI JP19H05801 (to S.S.), Exploratory Research Center on Life and Living Systems (ExCELLS) Grant 18-204 (to S.S.), Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI JP19H05416, JP18H04759, JP17H05992 and JP16H01442; JSPS KAKENHI JP17H01812 and JP15KT0076 (to S.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.