PNAS Nexus· 2026Q1
Programable extracellular matrix heterogeneity directs least-resistance migration in three dimensions
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- Q1SCImago
- 2026year
Short summary
A new light-guided method allows researchers to create micron-scale, programmable stiffness variations in 3D collagen matrices, revealing that cells navigate these environments by following paths of least resistance, not direct physical barriers.
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Key points
- A novel light-guided photopatterning method enables programmable control of ECM mechanics in 3D collagen networks.
- Localized stiffness increases of up to fivefold were achieved, creating sharp mechanical gradients.
- Cell migration is suppressed by these stiff barriers, but invasion is governed by long-range mechanical modulation, not steric hindrance.
- Cells integrate nonlocal mechanical cues to alter their migratory phenotype when navigating heterogeneous environments.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Cell migration through three-dimensional (3D) extracellular matrices (ECMs) is central to development, immune response, and cancer metastasis, yet how cells navigate mechanically heterogeneous environments remains poorly understood. Here we introduce a light-guided in situ ECM photopatterning method that enables micron-scale, programmable modulation of matrix mechanics within 3D collagen networks. Using this platform, we engineer well-defined mechanical barriers around tumor spheroids. Both bulk rheology and micromechanical measurements show photocrosslinking increases local stiffness by up to fivefold, creating sharp mechanical gradients. Strikingly, even small localized barriers strongly suppress cell dissemination over extended spatial ranges, far exceeding their geometric footprint. Systematic variation of barrier geometry reveals that invasion is not governed by direct steric obstruction but by long-range mechanical modulation of the ECM, which reshapes least-resistance migration paths and is tightly coupled to transitions in migratory phenotype. These results establish a quantitative framework for how microscale mechanical heterogeneity directs collective invasion and suggest that cancer cells integrate nonlocal mechanical cues to modulate their phenotype transitions when navigating complex environments.
The authors' abstract, as published at the source. PNAS Nexus, 2026 · DOI ↗
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Field: Cell Biology
Cell BiologyBiochemistry, Genetics and Molecular Biology