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Contact inhibition of locomotion (CIL), in which cells repolarize and move away from contact, is now established as a fundamental driving force in development, repair, and disease biology. Much of what we know of CIL stems from studies on two-dimensional (2D) substrates that do not provide an essential biophysical cue—the curvature of extracellular matrix fibers. We discover rules controlling outcomes of cell–cell collisions on suspended nanofibers and show them to be profoundly different from the stereotyped CIL behavior on 2D substrates. Two approaching cells attached to a single fiber do not repolarize upon contact but rather usually migrate past one another. Fiber geometry modulates this behavior; when cells attach to two fibers, reducing their freedom to reorient, only one cell repolarizes on contact, leading to the cell pair migrating as a single unit. CIL outcomes also change when one cell has recently divided and moves with high speed—cells more frequently walk past each other. Our computational model of CIL in fiber geometries reproduces the core qualitative results of the experiments robustly to model parameters. Our model shows that the increased speed of postdivision cells may be sufficient to explain their increased walk-past rate. We also identify cell–cell adhesion as a key mediator of collision outcomes. Our results suggest that characterizing cell–cell interactions on flat substrates, channels, or micropatterns is not sufficient to predict interactions in a matrix—the geometry of the fiber can generate entirely new behaviors.
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This content will become publicly available on September 18, 2026
Cell mechanics, environmental geometry, and cell polarity control cell–cell collision outcomes
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.
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- Award ID(s):
- 2119948
- PAR ID:
- 10648453
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 21
- Issue:
- 36
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 7074 to 7090
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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