What is it about?
Cells that line our organs can move together like a flowing liquid or settle into a stable, tightly packed layer. This transition resembles a traffic jam, but what tells crowded cells to slow down? We studied laboratory-grown cell layers and found that changes in nutrient processing help regulate this transition. A key player is pyruvate, a substance produced when cells break down sugar. Restricting its entry into mitochondria, structures that process nutrients and supply energy, kept crowded cells moving and exchanging neighbors for longer. This sustained movement required the cells’ internal force-generating machinery and increased uptake of surrounding fluid through large “gulps,” a process called macropinocytosis. Blocking this fluid uptake removed the increase in movement. Together, these findings connect nutrient processing inside cells to the collective behavior of an entire cell layer.
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Why is it important?
The ability to switch between movement and stability is essential for building organs, repairing wounds, and maintaining protective tissue barriers. Our study identifies a biological mechanism that helps control this switch: a connection between mitochondrial nutrient processing, cellular forces, and fluid uptake. We found that restricting mitochondrial pyruvate entry increased cell movement without substantially changing overall energy production. This shows that the route nutrients take inside cells can help regulate how a cell layer behaves. The findings provide a foundation for investigating how metabolic changes influence tissue repair and diseases involving abnormal cell movement, including cancer invasion.
Perspectives
As an engineer, I am fascinated by how processes inside individual cells give rise to the physical behavior of an entire tissue. What excites me about this study is that changing where a nutrient goes inside cells can keep a crowded cell layer moving. Bringing together physics, cell biology, and metabolism helped us uncover this connection. I hope this work encourages researchers to consider nutrient processing as an active part of how tissues organize themselves, coordinate movement, and establish stability.
Neil Lin
University of California Los Angeles
Read the Original
This page is a summary of: Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis, Proceedings of the National Academy of Sciences, October 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2617216123.
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