Microtubule lattice dynamics in response to mechanical loading

Figure caption: Tubulin incorporation into bent MTs. Left: Bent end-stabilized MT (purple) under the TIRF microscope. Tubulin incorporation into the shaft is visible as green stretches. Right: Tubulin incorporation frequency depending on the local curvature and on the distance from the point of highest curvature. The purple dotted line indicates the tubulin incorporation frequency into straight MTs.

Microtubules (MTs) are dynamic structural components of cells, essential for many processes like cell division, intracellular transport, and motility. MTs are dissipative polymers, which grow and shrink by dimer addition and removal at their extremities. The dissipative nature of the MT tip dynamics, called dynamic instability, is central to many cellular processes and has been studied extensively over the past 30 years. In contrast, little is known about the MT lattice dynamics far away from the tips, which have been considered until recently as frozen and inert structures. In living cells, MTs experience mechanical loads through interactions with molecular motors or cellular deformations, often resulting in significant bending. This positions MTs as potential mechanosensors that respond to the cell’s mechanical environment.

Our project aims to use coarse-grained molecular dynamics simulations to investigate how stress and strain propagate along the MT shaft under mechanical loading, examining their effects on lattice plasticity and tubulin exchange. The theoretical study is accompanied by controlled in vitro experiments on the MT response under loading in the group of L. Schaedel (U. Saarbrücken). Our study aims to clarify two points,

(i) is mechanical loading able to induce lattice plasticity in the canonical MT structure (without compromising overall MT stability)

and (ii) what is the role of topological defects in the MT response to mechanical loading.

From a biological perspective our study is expected to provide valuable insights into how the MT network adapts to mechanical stress to support cellular function.

FUNDING

Tec 21