Chew, Wei-XiangNédélec, FrançoisSurrey, Thomas2025-09-042025-09-042025Chew 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.24221901220027-8424http://hdl.handle.net/10230/71104During 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.application/pdfengCopyright © 2025 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1073/pnas.2422190122Active matterBipolar spindleComputer simulationMicrotubule networkMotor proteinsinfo:eu-repo/semantics/openAccess