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A floor-field model of tau-taxol competition explains tau envelope dynamics on taxol-stabilized microtubules

Chevalier, C.; Siahaan, V.; Grover, R.; Diez, S.; Santen, L.

2024-11-21 biophysics
10.1101/2024.11.19.624338 bioRxiv
Show abstract

Tau is a microtubule-associated protein (MAP) that is highly expressed in neurons. Recent in-vitro studies have shown that tau molecules can segregate into cohesive envelopes on paclitaxel (taxol) stabilized microtubules. These envelopes act as selective barriers gating the motor transport and protecting microtubules against the action of severing enzymes. However, the mechanisms underlying the formation of these envelopes remain unclear. Recent in vitro reconstitution assays revealed that the formation of tau envelopes induces a compaction of the underlying microtubule lattice, whereas taxol binding induces lattice expansion, indicating competitive binding between tau and taxol on microtubules. In this study, we use physical modeling to investigate how this competition between tau and taxol regulates the formation of tau envelopes. Our model includes static and dynamic floor-fields, concepts adapted from pedestrian dynamics. By comparing our simulation results with experimental data, we demonstrate that tau-taxol competition on the microtubule lattice is sufficient to explain the features of the formation and disassembly of tau envelopes. Notably, tau-tau interactions are not necessary to account for the steadiness of these envelopes.

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