Edge curvature drives endoplasmic reticulum reorganization and dictates epithelial migration mode

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Conflicts of Interest

Identified Weaknesses

Rating Explanation

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Paper Summary

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Cells Feel the Curve: How Wound Shape Guides Healing

This study reveals that the endoplasmic reticulum (ER), a network-like structure inside cells, changes shape depending on the curve of a wound edge, influencing how cells move to close it. At outward-curving edges, ER forms tubes and promotes crawling, while at inward-curving edges, it forms sheets and encourages tightening. This shape-shifting ER guides the orientation of cell-substrate attachments, thus controlling the migration mode.

Possible Conflicts of Interest

None identified.

Identified Weaknesses

Limited in vivo validation

While the study provides compelling evidence in cell cultures and mouse skin, further research is needed to confirm these findings in living organisms and explore the long-term implications for wound healing in different contexts.

Focus on a single cell type

The study focuses on epithelial cells, which are only one type of cell involved in wound healing. The role of other cell types, like fibroblasts and immune cells, and their interaction with the ER in curvature-driven migration requires further investigation.

Simplified mathematical model

Although the mathematical model provides a framework for understanding ER morphology based on strain energy minimization, it simplifies complex biological processes. Incorporating other factors and validating the model's predictions experimentally would enhance its robustness.

Rating Explanation

This study provides strong evidence for a novel mechanism linking wound geometry to intracellular organization and cell migration. The combination of experimental and computational approaches, along with the use of multiple model systems, makes a compelling case for the role of the ER in dictating migration modes. Although further in vivo validation and exploration of broader cell type involvement are needed, the current findings significantly advance our understanding of wound healing.

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