Brownian dynamics modeling of microtubule force generation

Gudimchuk N.B., Ulyanov E.V.1, Vinogradov D.S.1, Ataullakhanov F.I.2

Center for Theoretical Problems of Physico-Chemical Pharmacology RAS, Russia, 119991, Moscow, ul. Kosygin 4; Tel: (495) 938-25-33, fax: (495) 938-25-33

1Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology, Russia, 117997, Moscow, Samory Machel St., 1. Phone: (495) 287-65-70, fax: (495) 664-70-90

2Faculty of Physics, Lomonosov Moscow State University, Russia, 119991, Moscow, ul. Lenin Hills, 1, p. 2 Tel .: (495) 939-16-82, fax: (495) 932-88-20

Microtubules are intracellular polymers of tubulin protein, which are necessary for transport, mobility, division and maintenance of cell structure. Due to its key property of dynamic instability - the ability to switch between phases of growth and shortening, microtubules can develop pulling and pushing forces ranging in magnitude from several units to tens of piconewtons. These forces play an important role for the positioning of organelles within the cell, for the centering of the mitotic spindle and the movement of chromosomes during cell division.

We have created a coarse-grained molecular model of a microtubule based on the Brownian dynamics method, which allows for the first time to simultaneously describe the assembly, disassembly of microtubules, the structure of their ends, as well as the ability of microtubules to generate pulling and pushing forces. The analysis of the model revealed unexpected characteristics of tubulin-tubulin interactions, such as, for example, the presence of a significant activation barrier in lateral bonds. A previously unknown mechanism for coupling the ends of growing microtubules with chromosomes under mechanical load follows from the model. Our study sheds light on one of the long-standing unresolved problems of the mechanism of synchronization of growing and shortening microtubules during chromosomal oscillations in mitosis.

The work was performed using the equipment of the Center for the collective use of ultrahigh-performance computing resources of Moscow State University Lomonosov supported by a grant from the Russian Science Foundation, project No. 17-74-20152.

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