Mechanical coupling coordinates microtubule growth
During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to be...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/89467 |
| _version_ | 1797374768731652096 |
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| author | Bonnibelle K Leeds Katelyn F Kostello Yuna Y Liu Christian R Nelson Sue Biggins Charles L Asbury |
| author_facet | Bonnibelle K Leeds Katelyn F Kostello Yuna Y Liu Christian R Nelson Sue Biggins Charles L Asbury |
| author_sort | Bonnibelle K Leeds |
| collection | DOAJ |
| description | During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes. |
| first_indexed | 2024-03-08T19:09:32Z |
| format | Article |
| id | doaj.art-4802c6d4179049c2934ea6eb8091dffd |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T19:09:32Z |
| publishDate | 2023-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4802c6d4179049c2934ea6eb8091dffd2023-12-27T17:11:12ZengeLife Sciences Publications LtdeLife2050-084X2023-12-011210.7554/eLife.89467Mechanical coupling coordinates microtubule growthBonnibelle K Leeds0https://orcid.org/0009-0009-8932-707XKatelyn F Kostello1Yuna Y Liu2Christian R Nelson3https://orcid.org/0000-0001-8717-0229Sue Biggins4https://orcid.org/0000-0002-4499-6319Charles L Asbury5https://orcid.org/0000-0002-0143-5394Department of Physiology & Biophysics, University of Washington, Seattle, United StatesDepartment of Physiology & Biophysics, University of Washington, Seattle, United StatesDepartment of Physiology & Biophysics, University of Washington, Seattle, United StatesBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Physiology & Biophysics, University of Washington, Seattle, United StatesDuring mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes.https://elifesciences.org/articles/89467mitosisspindlek-fiberkinetochoredynamic instabilitymechanobiology |
| spellingShingle | Bonnibelle K Leeds Katelyn F Kostello Yuna Y Liu Christian R Nelson Sue Biggins Charles L Asbury Mechanical coupling coordinates microtubule growth eLife mitosis spindle k-fiber kinetochore dynamic instability mechanobiology |
| title | Mechanical coupling coordinates microtubule growth |
| title_full | Mechanical coupling coordinates microtubule growth |
| title_fullStr | Mechanical coupling coordinates microtubule growth |
| title_full_unstemmed | Mechanical coupling coordinates microtubule growth |
| title_short | Mechanical coupling coordinates microtubule growth |
| title_sort | mechanical coupling coordinates microtubule growth |
| topic | mitosis spindle k-fiber kinetochore dynamic instability mechanobiology |
| url | https://elifesciences.org/articles/89467 |
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