BPS2026 – Inference of molecular-scale mechanisms of PRC1 resistance to microtubule pair separation

The regulation of a passive crosslinking protein in mitotic spindle formation, PRC1, has been previously found in gliding assay experiments to resist microtubule sliding of antiparallel pairs via two distinct modes. To explore the possible mechanisms, we developed a computational model with parameter fits capable of reproducing both modes seen in experiments. In the simulations, we found that the mode with greater slowing of microtubule separation was associated with a substantially smaller separation (15 nm) between the crosslinked microtubules than the mode with slighter slowing (30 nm). The closer separation allows the PRC1 force to be better aligned against sliding. We show how the closer separation is associated with the experimentally observed formation of PRC1 clusters near the edge of the microtubule overlap zone, and explore the factors which induce or dissipate this clustering. The computational model uses the CyLaKS framework, with the microtubule dynamics in a gliding assay configuration described by a mean field reduction of a stochastic model for the driving by kinesin molecules in response to the resisting PRC1 force. This work was partially supported via NSF DMS grants 2153399 and 2153374, and via NIH/NIGMS grant R01GM149782.