Emerging techniques bring new understanding to how cells navigate confined spaces
DOI: 10.1063/10.0047512
Emerging techniques bring new understanding to how cells navigate confined spaces lead image
How cells migrate is crucial to understanding a wide range of biological processes, from wound healing to metastasis. Migration in confined spaces less than 20 micrometers has been found to be particularly important for understanding how cancer spreads. New techniques such as 3D in vitro models and computational tools have provided new methods and potential synergies for examining cell migration in confined spaces.
Quinones et al. survey advances in in vitro bioengineered platforms and mathematical models to study the mechanisms of confined migration. Taking stock of techniques using polydimethylsiloxane (PDMS) and microprinting as well as molecular, cellular-scale, and multi-cellular scale models, the group’s analysis highlights what emerging techniques can offer and identifies next steps for mechanistic testing.
“Cell migration in the body requires cells to move in constricted environments in a 3D context,” said author Joseph Chen. “Current experimental approaches are limited in the examination of how these mechanisms interact at broader scales, especially over time. Computational approaches are a logical next step.”
PDMS, for example, enables studies like post-pinch experiments, which reveal how the cytoskeleton aids the nucleus — a cell’s largest and stiffest component — in squeezing through tight spaces, and how DNA might repair after such stress. Microprinted islands of cell adhesion show how cells sense and respond to variations of substrate rigidity in their microenvironments.
These mechanistic insights can be integrated into computational models at various scales (molecular, cellular, and multi-cellular) to predict cell migration speeds and nuclear deformation, revealing confined migration patterns in various contexts.
The group next looks to the influence of confinement on a cell’s epigenome to determine how cells might code in “memories” of confinement scenarios.
Source: “Confined cell migration: Insights from in vitro and in silico methodologies,” by Wyatt Quinones, Jackson Huse, Dylan A. Goodin, Zoe Lung, Landon Teer, Hermann B. Frieboes, and Joseph Chen, Biophysics Reviews (2026). The article can be accessed at https://doi.org/10.1063/5.0297695