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Reciprocal regulation of cellular mechanics and metabolism

Abstract

Metabolism and mechanics are intrinsically intertwined. External forces, sensed through the cytoskeleton or distortion of the cell and organelles, induce metabolic changes in the cell. The resulting changes in metabolism, in turn, feed back to regulate every level of cell biology, including the mechanical properties of cells and tissues. Here we examine the links between metabolism and mechanics, highlighting signalling pathways involved in the regulation and response to cellular mechanosensing. We consider how forces and metabolism regulate one another through nanoscale molecular sensors, micrometre-scale cytoskeletal networks, organelles and dynamic biomolecular condensates. Understanding this cross-talk will create diagnostic and therapeutic opportunities for metabolic disorders such as cancer, cardiovascular pathologies and obesity.

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Fig. 1: Polymerization of haemoglobin drives sickle cell formation.
Fig. 2: Intracellular mechanosensation pathways that accelerate glycolysis.
Fig. 3: Reciprocal regulation of phase separation and cellular metabolism.
Fig. 4: Reciprocal regulation of mechanics and metabolism in cancer.
Fig. 5: Integration of metabolic technologies with force spectroscopy modalities correlates metabolic profiles to mechanics at different scales and in variable conditions.

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Acknowledgements

A.M. and T.M.J.E acknowledge support by the Netherlands Organization for Scientific Research (NWO-TTW, grant number 16249). L.J.H. was supported by the National Institutes of Health (R01GM132447 and R37CA240765), the Pershing Square Sohn Cancer Research Alliance and the American Cancer Society.

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A.M. conceived and supervised the project. T.M.J.E. performed the literature search and analysis. T.M.J.E., L.J.H., S.A. and A.M. contributed to writing of the initial draft and the subsequent revisions.

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Correspondence to Alireza Mashaghi.

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Peer review information Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editor: George Caputa.

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Evers, T.M.J., Holt, L.J., Alberti, S. et al. Reciprocal regulation of cellular mechanics and metabolism. Nat Metab 3, 456–468 (2021). https://doi.org/10.1038/s42255-021-00384-w

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