Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure

Author:

Long Alexandra F.123ORCID,Suresh Pooja423ORCID,Dumont Sophie14235ORCID

Affiliation:

1. Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA

2. Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA

3. Department of Bioengineering and Therapeutic Science, University of California, San Francisco, San Francisco, CA

4. Biophysics Graduate Program, University of California, San Francisco, San Francisco, CA

5. Chan Zuckerberg Biohub, San Francisco, CA

Abstract

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus and minus ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.

Funder

National Institutes of Health

National Science Foundation

NSF

Rita Allen Foundation

Searle Scholars Program

University of California, San Francisco

Publisher

Rockefeller University Press

Subject

Cell Biology

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