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Connections distributed within 3 μm of chromosomes are necessary and sufficient for the kinetochore-fiber’s robust anchorage in the mammalian spindle

Suresh, Pooja and Galstyan, Vahe and Phillips, Rob and Dumont, Sophie (2022) Connections distributed within 3 μm of chromosomes are necessary and sufficient for the kinetochore-fiber’s robust anchorage in the mammalian spindle. Biophysical Journal, 121 (3). 448a-449a. ISSN 0006-3495. doi:10.1016/j.bpj.2021.11.536. https://resolver.caltech.edu/CaltechAUTHORS:20220422-231443172

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Abstract

In mammalian cells, kinetochore-fibers are responsible for moving chromosomes within the spindle. To perform this task, they must generate and respond to forces while maintaining their connection to the spindle. Yet, how and where along their length they are anchored in the spindle, and which connections are necessary and sufficient remains unknown. Recent advances using microneedle manipulation opened new avenues in directly challenging kinetochore-fiber anchorage and revealed that anchorage near chromosomes restricts kinetochore-fiber pivoting there. To determine the components of this anchorage necessary and sufficient to locally restrict pivoting and maintain kinetochore-fiber orientation in the spindle center under force, we develop a theoretical framework using Euler-Bernoulli beam theory. We determine that highly localized anchorage just at the chromosome end fails to preserve kinetochore-fiber orientation in the spindle center. Similarly, global uniform anchorage fails to capture the localized resistance to pivoting by uniformly preserving structure everywhere. Instead, we show that local anchorage distributed within 3 μm of chromosomes is both necessary and sufficient for kinetochore-fibers to locally preserve their orientation under force. Together, our work indicates that while kinetochore-fibers have connections all along their length, not all connections are mechanically equivalent. Our model establishes the relationship between spindle architecture and the mechanics underlying kinetochore-fiber anchorage, and can be expanded to diverse spindle architectures across evolution.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.bpj.2021.11.536DOIArticle
ORCID:
AuthorORCID
Suresh, Pooja0000-0002-7793-4827
Galstyan, Vahe0000-0001-7073-9175
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2021 Biophysical Society. Published by Elsevier Inc. Available online 11 February 2022, Version of Record 11 February 2022.
Issue or Number:3
DOI:10.1016/j.bpj.2021.11.536
Record Number:CaltechAUTHORS:20220422-231443172
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220422-231443172
Official Citation:Pooja Suresh, Vahe Galstyan, Rob Phillips, Sophie Dumont, Connections distributed within 3 μm of chromosomes are necessary and sufficient for the kinetochore-fiber’s robust anchorage in the mammalian spindle, Biophysical Journal, Volume 121, Issue 3, Supplement 1, 2022, Pages 448a-449a, ISSN 0006-3495, https://doi.org/10.1016/j.bpj.2021.11.536.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114442
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Apr 2022 18:27
Last Modified:25 Apr 2022 18:27

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