Molecular design principles for bipolar spindle organization by two opposing motors

Chew, Wei-Xiang; Nédélec, François; Surrey, Thomas

Molecular design principles for bipolar spindle organization by two opposing motors

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dc.contributor.author Chew, Wei-Xiang
dc.contributor.author Nédélec, François
dc.contributor.author Surrey, Thomas
dc.date.accessioned 2025-09-04T06:39:23Z
dc.date.available 2025-09-04T06:39:23Z
dc.date.issued 2025
dc.description.abstract During cell division in animal cells, a bipolar spindle assembles to segregate the chromosomes. Various motor proteins with different properties are essential for spindle self-organization. The minimal set of components required to organize dynamic microtubules into a bipolar network remains however unknown. Here, we use computer simulations to explore whether two types of microtubule-crosslinking motors with opposite directionality can organize dynamic microtubules into bipolar spindles in three-dimensional space around a local microtubule nucleation source. We find that two motors are indeed sufficient, provided their properties resemble the main human spindle motors kinesin-5 and dynein, revealing the core mechanism of spindle self-organization. It is based on the synergistic interplay of a slow plus-directed symmetric motor and a fast minus-directed asymmetric motor. A hypothetical symmetric minus-directed motor can also support spindle formation together with kinesin-5, but only in a limited and unphysiological parameter range. In agreement with its accessory role in human cells, a minus motor with human kinesin-14 properties does not assemble stable bipolar spindles together with kinesin-5. These results reveal fundamental principles for the self-organization of dynamic bipolar microtubule architectures and highlight how distinct molecular designs of mitotic motors are optimized for their task.
dc.description.sponsorship Simulations were performed on the high-performance computing cluster at the Centre for Genomic Regulation in Barcelona, Spain. We acknowledge support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033), and the Generalitat de Catalunya through the CERCA programme. This project received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 951430; F.N. and T.S.) and received support from the Spanish Ministry of Science and Innovation, the State Research Agency and FEDER (grant PID2022-142927NB-I00/MCIN/AEI/10.13039/501100011033/FEDER, UE; T.S.). W.-X.C. was supported by a Human Frontier Science Program fellowship (HFSP LT000682/2020-C). F.N. was supported by the Gatsby Charitable Foundation. We thank Zoë Geraghty, Wei Ming Lim, and Aritra Sen for comments on the manuscript.
dc.format.mimetype application/pdf
dc.identifier.citation Chew WX, Nédélec F, Surrey T. Molecular design principles for bipolar spindle organization by two opposing motors. Proc Natl Acad Sci U S A. 2025 Mar 25;122(12):e2422190122. DOI: 10.1073/pnas.2422190122
dc.identifier.doi http://dx.doi.org/10.1073/pnas.2422190122
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10230/71104
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A. 2025 Mar 25;122(12):e2422190122
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/951430
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-142927NB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Active matter
dc.subject.keyword Bipolar spindle
dc.subject.keyword Computer simulation
dc.subject.keyword Microtubule network
dc.subject.keyword Motor proteins
dc.title Molecular design principles for bipolar spindle organization by two opposing motors
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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