Physical properties of the cytoplasm modulate the rates of microtubule polymerization and depolymerization

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molines, A. T., Lemière, J., Gazzola, M., Steinmark, I. E., Edrington, C. H., Hsu, C.-T., Real-Calderon, P., Suhling, K., Goshima, G., Holt, L. J., Thery, M., Brouhard, G. J., & Chang, F. Physical properties of the cytoplasm modulate the rates of microtubule polymerization and depolymerization. Developmental Cell, 57(4), (2022): 466-479.e6, https://doi.org/10.1016/j.devcel.2022.02.001.
The cytoplasm is a crowded, visco-elastic environment whose physical properties change according to physiological or developmental states. How the physical properties of the cytoplasm impact cellular functions in vivo remains poorly understood. Here, we probe the effects of cytoplasmic concentration on microtubules by applying osmotic shifts to fission yeast, moss, and mammalian cells. We show that the rates of both microtubule polymerization and depolymerization scale linearly and inversely with cytoplasmic concentration; an increase in cytoplasmic concentration decreases the rates of microtubule polymerization and depolymerization proportionally, whereas a decrease in cytoplasmic concentration leads to the opposite. Numerous lines of evidence indicate that these effects are due to changes in cytoplasmic viscosity rather than cellular stress responses or macromolecular crowding per se. We reconstituted these effects on microtubules in vitro by tuning viscosity. Our findings indicate that, even in normal conditions, the viscosity of the cytoplasm modulates the reactions that underlie microtubule dynamic behaviors.
This work was supported by grants to F.C. (NIH GM115185, NIH GM056836, NIH GM146438), to L.J.H. (American Cancer Society RSG-19-073-01-TBE, Pershing Square Sohn Cancer Award, Chan Zuckerberg Initiative, NIH GM132447 and NIH CA240765), to G.G. (JSPS KAKENHI 17H06471 and 18KK0202), to K.S. (UK’s Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/R004803/1) and to M.T. (ERC Consolidator Grant 771599). I.E.S. was supported by King’s College London through a LIDo (London Interdisciplinary Doctoral programme) iCASE studentship.