Mechanics of Multicentrosomal Clustering in Bipolar Mitotic Spindles.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
21 07 2020
21 07 2020
Historique:
received:
17
12
2019
revised:
06
04
2020
accepted:
04
06
2020
pubmed:
2
7
2020
medline:
15
5
2021
entrez:
2
7
2020
Statut:
ppublish
Résumé
To segregate chromosomes in mitosis, cells assemble a mitotic spindle, a molecular machine with centrosomes at two opposing cell poles and chromosomes at the equator. Microtubules and molecular motors connect the poles to kinetochores, specialized protein assemblies on the centromere regions of the chromosomes. Bipolarity of the spindle is crucial for the proper cell division, and two centrosomes in animal cells naturally become two spindle poles. Cancer cells are often multicentrosomal, yet they are able to assemble bipolar spindles by clustering centrosomes into two spindle poles. Mechanisms of this clustering are debated. In this study, we computationally screen effective forces between 1) centrosomes, 2) centrosomes and kinetochores, 3) centrosomes and chromosome arms, and 4) centrosomes and cell cortex to understand mechanics that determines three-dimensional spindle architecture. To do this, we use the stochastic Monte Carlo search for stable mechanical equilibria in the effective energy landscape of the spindle. We find that the following conditions have to be met to robustly assemble the bipolar spindle in a multicentrosomal cell: 1) the strengths of centrosomes' attraction to each other and to the cell cortex have to be proportional to each other and 2) the strengths of centrosomes' attraction to kinetochores and repulsion from the chromosome arms have to be proportional to each other. We also find that three other spindle configurations emerge if these conditions are not met: 1) collapsed, 2) monopolar, and 3) multipolar spindles, and the computational screen reveals mechanical conditions for these abnormal spindles.
Identifiants
pubmed: 32610087
pii: S0006-3495(20)30474-4
doi: 10.1016/j.bpj.2020.06.004
pmc: PMC7376091
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
434-447Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM121971
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM130298
Pays : United States
Informations de copyright
Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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