Multi-kinesin clusters impart mechanical stress that reveals mechanisms of microtubule breakage in cells DOI Creative Commons
Qi Geng, Alejandro Santana‐Bonilla,

Siara N. Sandwith

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Microtubules are cytoskeletal filaments that provide structural support for numerous cellular processes. Despite their high rigidity, microtubules can be dramatically bent in cells and it is unknown how much force a microtubule withstand before breaking. We find liquid-liquid phase separation of the kinesin-3 motor KIF1C results multi-kinesin clusters entangle neighboring impose level mechanical stress breakage disassembly. Combining computational simulations experiments, we show fragmentation enhanced by having highly processive kinesin domain, stiff clustering mechanism, sufficient drag on microtubules. estimate rupture 70-120 pN, which lower than previous estimates based vitro studies with taxol-stabilized These indicate presence multiple kinesins cargo has potential to cause breakage. propose mechanisms exist protect integrity releasing either motor-cargo or motor-microtubule interaction, thereby preventing accumulation upon engagement multi-motor

Language: Английский

Multi-kinesin clusters impart mechanical stress that reveals mechanisms of microtubule breakage in cells DOI Creative Commons
Qi Geng, Alejandro Santana‐Bonilla,

Siara N. Sandwith

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Microtubules are cytoskeletal filaments that provide structural support for numerous cellular processes. Despite their high rigidity, microtubules can be dramatically bent in cells and it is unknown how much force a microtubule withstand before breaking. We find liquid-liquid phase separation of the kinesin-3 motor KIF1C results multi-kinesin clusters entangle neighboring impose level mechanical stress breakage disassembly. Combining computational simulations experiments, we show fragmentation enhanced by having highly processive kinesin domain, stiff clustering mechanism, sufficient drag on microtubules. estimate rupture 70-120 pN, which lower than previous estimates based vitro studies with taxol-stabilized These indicate presence multiple kinesins cargo has potential to cause breakage. propose mechanisms exist protect integrity releasing either motor-cargo or motor-microtubule interaction, thereby preventing accumulation upon engagement multi-motor

Language: Английский

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