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Updated: Aug 5, 2026
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Concentric Gel System to Study the Biophysical Role of Matrix Microenvironment on 3D Cell Migration
Published on: April 3, 2015
Microscale matrix defects suppress tension-dependent protrusions and stall collective cell migration
Hannah Zmuda1, Diego Barra Avila1, Ping-Hsien Lee1
1Department of Biomedical Engineering, Washington University, St. Louis, MO, USA.
Cell Reports
|July 31, 2026
Summary
Epithelial cells collectively migrating can stall over large distances when encountering micro-defects, due to cytoskeletal disruption propagating between cells. This multicellular response is modulated by extracellular matrix properties and cell biophysics.
Area of Science:
- Biophysics
- Cell Biology
- Tissue Engineering
Background:
- Epithelial cells must detect and respond to extracellular defects for coordinated migration during development, wound repair, and disease.
- Understanding the biophysical mechanisms of cell-matrix interactions is crucial for tissue homeostasis and regeneration.
Purpose of the Study:
- To investigate how collectively migrating epithelia respond to micro-defects.
- To elucidate the role of extracellular matrix components and cell biophysical properties in regulating epithelial cell migration and defect sensing.
Main Methods:
- Utilized laser ablation to create controlled micro-defects in migrating epithelial sheets.
- Manipulated extracellular matrix properties (stiffness, collagen type, osmolarity) and measured cell biophysical parameters (stiffness, membrane tension).
- Observed and quantified multicellular stalling responses and cytoskeletal disruption propagation.
Main Results:
- Collectively migrating epithelia exhibited large-scale spatiotemporal stalling in response to micro-defects, particularly with collagen type IV.
- Local cytoskeletal disruption at the leading edge propagated to follower cells, causing multicellular stalling over larger scales.
- Cell stiffness and membrane tension, regulated by extracellular cues, influenced protrusive activity and migration stalling.
- Softer matrices, collagen-IV, and hypertonic media enhanced defect sensing and multicellular stalling.
Conclusions:
- Extracellular cues significantly influence epithelial cell biophysics, impacting their ability to sense and respond to micro-defects.
- Intercellular propagation of cytoskeletal disruption is a key mechanism for large-scale multicellular responses to local defects.
- Collagen-IV, softer matrices, and hypertonic conditions enhance epithelial wound detection and repair through improved sensing.
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