Cell state-specific cytoplasmic density controls spindle architecture and scaling

Kletter T, Muñoz O, Reusch S, Biswas A, Halavatyi A, Neumann B, Kuropka B, Zaburdaev V, Reber S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nature Cell Biology Nature Research

DOI: 10.1038/s41556-025-01678-x

Abstract

Mitotic spindles are dynamically intertwined with the cytoplasm they assemble in. How the physicochemical properties of the cytoplasm affect spindle architecture and size remains largely unknown. Using quantitative biochemistry in combination with adaptive feedback microscopy, we investigated mitotic cell and spindle morphology during neural differentiation of embryonic stem cells. While tubulin biochemistry and microtubule dynamics remained unchanged, spindles changed their scaling behaviour; in differentiating cells, spindles were considerably smaller than those in equally sized undifferentiated stem cells. Integrating quantitative phase imaging, biophysical perturbations and theory, we found that as cells differentiated, their cytoplasm became more dilute. The concomitant decrease in free tubulin activated CPAP (centrosomal P4.1-associated protein) to enhance the centrosomal nucleation capacity. As a consequence, in differentiating cells, microtubule mass shifted towards spindle poles at the expense of the spindle bulk, explaining the differentiation-associated switch in spindle architecture. This study shows that cell state-specific cytoplasmic density tunes mitotic spindle architecture. Thus, we reveal physical properties of the cytoplasm as a major determinant in organelle size control.

Involved external institutions

Max-Planck-Institut für Infektionsbiologie / Max Planck Institute for Infection Biology DE Germany (DE) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Humboldt-Universität zu Berlin DE Germany (DE) European Molecular Biology Laboratory (EMBL) DE Germany (DE) Freie Universität Berlin DE Germany (DE)

How to cite

APA:

Kletter, T., Muñoz, O., Reusch, S., Biswas, A., Halavatyi, A., Neumann, B.,... Reber, S. (2025). Cell state-specific cytoplasmic density controls spindle architecture and scaling. Nature Cell Biology. https://doi.org/10.1038/s41556-025-01678-x

MLA:

Kletter, Tobias, et al. "Cell state-specific cytoplasmic density controls spindle architecture and scaling." Nature Cell Biology (2025).

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