What is it about?

Cells often work together to move in large groups—a crucial process in the development of embryos, healing of wounds, and spreading of some cancers. During this movement, known as collective cell migration, cells stay mechanically connected to each other to coordinate their motion. This type of long-range coordination requires cells to continuously adapt the forces they exert on their neighbors. How cells accomplish this is not well understood, hindering efforts to control cell migration for therapeutic or engineering purposes. To address this, we investigated the interplay between mechanical forces and biochemical regulation with molecular and cell scale experiments and mathematical models bridging them. Using molecular sensors that measure the forces on specific proteins at the cell-cell contacts, we found that the biochemical regulation of a key mechanical protein, vinculin, toggles it between closed, unloaded and open, loaded states. This controls the forces it transmits at cell-cell contacts during migration. Combining molecular perturbations and quantitative measurements of cell migration, we show that this biochemical switch controls the speed and coordination of collective cell migration. Together, this work uncovers how mechanical forces and biochemical regulation interact to control multicellular dynamics.

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Why is it important?

Collective cell migration is important for the development and homeostasis of multicellular organisms as well as the progression of disease. It is an integrated biochemical and physical process, but a challenge is understanding how these components interact. This work uncovers how the biochemical regulation of a protein's mechanical function can control the long-range coordination of collective cell migration. It also establishes a framework for relating biochemical regulation, mechanical properties, and cell migration dynamics that enable new studies of other proteins and living systems. Uncovering how biochemical and physical elements interact to control cell migration will advance our fundamental understanding of biological processes and could lead to novel ways of manipulating cell migration for treating diseases or engineering tissues.

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This page is a summary of: Coupling during collective cell migration is controlled by a vinculin mechanochemical switch, Proceedings of the National Academy of Sciences, December 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2316456120.
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