HRZZ
Balance of forces and torques in the mitotic spindle — SpindleForceBalance
The mitotic spindle is a self-organized micro-machine composed of microtubules and the associated proteins, which divides genetic material between the two nascent daughter cells. Forces exist in the spindle throughout mitosis and are crucial for spindle functioning in each phase. In metaphase, the mitotic spindle has a recognizable shape with a characteristic arrangement of microtubules. Microtubules extend from the opposite spindle poles and interact with the chromosomes and with each other. Forces exerted by kinetochore microtubules keep the chromosomes under tension at the metaphase plate, which contributes to silencing of the spindle assembly checkpoint. In prometaphase, forces are orchestrated in such a way that leads to chromosome congression from a random position to the equatorial plane of the spindle. In anaphase the forces act in the opposite direction, towards the spindle poles. Thus, quantification of the direction and magnitude of forces in space and time is crucial for understanding of the functioning of the mitotic spindle. Though a significant progress in understanding the mechanics of the spindle is achieved, the question of force balance in the spindle is still under debate.
Interdisciplinary research, in which theoretical physicists and cell biologists work together on spindle mechanics is one of the most promising approaches nowadays. However, a small number of scientists in Croatia are working on this topic. This project will strengthen the scientific connections between them, as well as between their institutions, University of Zagreb and the Ruđer Bošković Institute in Zagreb.
Researcher (PI): Nenad Pavin
Host Institution (HI): University of Zagreb – Faculty of Science
Collaborators: Iva Tolić (PI), Arian Ivec (PhD student)
HRZZ call: Research Projects IP-2019-04
HrZZ funding: 1,000,000.00 HRK for four years
Project Number: IP-2019-04-5967
Starting date: February 1st, 2020
Publications
I. Ban, L. Tomašić, M. Trakala, I.M. Tolić and N. Pavin
Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes.
Biophys J 122, 632-645 (2023).
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Earlier version of the manuscript is available online at: bioRxiv, doi.org/10.1101/2022.04.14.488382.
P. Risteski, D. Božan, M. Jagrić, A. Bosilj, N. Pavin and I.M. Tolić
Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment.
Cell Reports 40, 111169 (2022)
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M. Trupinić, B. Kokanović, I. Ponjavić, I. Barišić, S. Šegvić, A. Ivec, I.M. Tolić
The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin.
Curr Biol 32 , 2480–2493 (2022).
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K. B. Velle, A. S. Kennard, M. Trupinić, A. Ivec, A. J. M. Swafford, E. Nolton, L. M. Rice, I. M. Tolić, L. K. Fritz-Laylin, P. Wadsworth
Naegleria’s mitotic spindles are built from unique tubulins and highlight core spindle features.
Curr Biol 32, 1247–1261 (2022).
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A. Ivec, M. Trupinić, I.M. Tolić and N. Pavin
Oblique circle method for measuring the curvature and twist of mitotic spindle microtubule bundles.
Biophys J 120, 3641-3648 (2021).
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P. Risteski, M. Jagrić, N. Pavin and I.M. Tolić
Biomechanics of chromosome alignment at the spindle midplane.
Curr Biol 31, R574-R585 (2021).
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I.M. Tolić and N. Pavin
Mitotic spindle: Lessons from theoretical modeling.
Mol Biol Cell 32, 218–222 (2021).
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N. Pavin and I.M. Tolić
Mechanobiology of the Mitotic Spindle.
Dev Cell 56, 192-201 (2021).
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