skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Multi-cell ECM compaction is predictable via superposition of nonlinear cell dynamics linearized in augmented state space
Award ID(s):
1762961
PAR ID:
10173133
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
PLOS Computational Biology
Volume:
15
Issue:
9
ISSN:
1553-7358
Page Range / eLocation ID:
e1006798
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Interactions between crawling cells, which are essential for many biological processes, can be quantified by measuring cell–cell collisions. Conventionally, experiments of cell–cell collisions are conducted on two-dimensional flat substrates, where colliding cells repolarize and move away upon contact with one another in ‘‘contact inhibition of locomotion’’ (CIL). Inspired by recent experiments that show cells on suspended nanofibers have qualitatively different CIL behaviors than those on flat substrates, we develop a phase field model of cell motility and two-cell collisions in fiber geometries. Our model includes cell–cell and cell–fiber adhesion, and a simple positive feedback mechanism of cell polarity. We focus on cell collisions on two parallel fibers, finding that larger cell deformability (lower membrane tension), larger positive feedback of polarization, and larger fiber spacing promote more occurrences of cells walking past one another. We can capture this behavior using a simple linear stability analysis on the cell–cell interface upon collision. 
    more » « less
  2. Successful development of tissue structures requires different collective cell migration patterns or phenotypes. Two examples of collective migration phenotypes in epithelial morphogenic processes, such as tubulogenesis, are rotational and invasive. Rotational collective migration phenotypes (RCM) typically lead to acinar structures, and invasive collective migration (ICM) phenotypes lead to duct-like structures. How cells adopt these different phenotypes is still largely unknown. Here, we investigate how cell–cell adhesion marker P-cadherin (CDH3) and mechanical cell–matrix interactions, including matrix deformations, protrusions, and focal adhesions, control rotational or invasive phenotypes during tubulogenesis. To accomplish our objective, we created a custom 3D microfluidic assay to perform live-cell imaging of epithelial clusters or cysts [wild-type (WT) and CDH3-depleted (CDH3-/-)] undergoing tubulogenesis, while simultaneously measuring matrix deformation rates. Our findings reveal WT epithelial cysts maintain rotational phenotypes, but transition to an invasive phenotype to undergo tubulogenesis. Furthermore, we demonstrate ICM phenotypes correlate with higher matrix deformation rates compared to rotational phenotypes. Our studies reveal CDH3 is required for epithelial cysts to transition from rotational to ICM phenotypes, associated with decreased matrix deformation rates. Without CDH3, epithelial cysts lose their ability to adopt ICM phenotypes, which can be rescued by RhoA activation. Finally, we demonstrate that the RhoA-rescued ICM phenotype is mediated, in part, by increased matrix deformation rates and vinculin recruitment to focal adhesion sites. 
    more » « less
  3. null (Ed.)
    The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell–cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following, and sliding past each other upon collision. Capitalizing on this large experimental dataset of coupled cell trajectories, we infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting noncancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit attraction and antifriction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types. 
    more » « less