Müller N, Kierfeld J
Department of Physics, TU Dortmund University, D-44221 Dortmund, Germany.
Phys Biol. 2014 Aug;11(4):046001. doi: 10.1088/1478-3975/11/4/046001. Epub 2014 Jun 4.
We introduce a model for microtubule (MT) mechanics containing lateral bonds between dimers in neighboring protofilaments, bending rigidity of dimers, and repulsive interactions between protofilaments modeling steric constraints to investigate the influence of mechanical forces on hydrolysis and catastrophes. We use the allosteric dimer model, where tubulin dimers are characterized by an equilibrium bending angle, which changes from 0° to 22° by hydrolysis of a dimer. This also affects the lateral interaction and bending energies and, thus, the mechanical equilibrium state of the MT. As hydrolysis gives rise to conformational changes in dimers, mechanical forces also influence the hydrolysis rates by mechanical energy changes modulating the hydrolysis rate. The interaction via the MT mechanics then gives rise to correlation effects in the hydrolysis dynamics, which have not been taken into account before. Assuming a dominant influence of mechanical energies on hydrolysis rates, we investigate the most probable hydrolysis pathways both for vectorial and random hydrolysis. Investigating the stability with respect to lateral bond rupture, we identify initiation configurations for catastrophes along the hydrolysis pathways and values for a lateral bond rupture force. If we allow for rupturing of lateral bonds between dimers in neighboring protofilaments above this threshold force, our model exhibits avalanche-like catastrophe events.
我们引入了一个微管（MT）力学模型，该模型包含相邻原纤维中二聚体之间的横向键、二聚体的弯曲刚度以及对空间位阻进行建模的原纤维之间的排斥相互作用，以研究机械力对水解和灾变的影响。我们使用变构二聚体模型，其中微管蛋白二聚体的特征在于平衡弯曲角度，该角度通过二聚体的水解从0°变为22°。这也会影响横向相互作用和弯曲能量，进而影响微管的机械平衡状态。由于水解会导致二聚体的构象变化，机械力也会通过调节水解速率的机械能变化来影响水解速率。通过微管力学的相互作用进而在水解动力学中产生相关效应，这在以前尚未被考虑到。假设机械能对水解速率有主要影响，我们研究了矢量水解和随机水解的最可能水解途径。通过研究横向键断裂的稳定性，我们确定了水解途径上灾变的起始构型以及横向键断裂力的值。如果我们允许在高于该阈值力的情况下相邻原纤维中二聚体之间的横向键断裂，我们的模型会表现出雪崩式的灾变事件。
