Department of Physics, University of Warwick, Coventry, United Kingdom.
Biophys J. 2010 Apr 21;98(8):1598-607. doi: 10.1016/j.bpj.2010.01.004.
The coupling between the depolymerization of microtubules (MTs) and the motion of the Dam1 ring complex is now thought to play an important role in the generation of forces during mitosis. Our current understanding of this motion is based on a number of detailed computational models. Although these models realize possible mechanisms for force transduction, they can be extended by variation of any of a large number of poorly measured parameters and there is no clear strategy for determining how they might be distinguished experimentally. Here we seek to identify and analyze two distinct mechanisms present in the computational models. In the first, the splayed protofilaments at the end of the depolymerizing MT physically prevent the Dam1 ring from falling off the end, and in the other, an attractive binding secures the ring to the microtubule. Based on this analysis, we discuss how to distinguish between competing models that seek to explain how the Dam1 ring stays on the MT. We propose novel experimental approaches that could resolve these models for the first time, either by changing the diffusion constant of the Dam1 ring (e.g., by tethering a long polymer to it) or by using a time-varying load.
现在认为微管（MTs）解聚与 Dam1 环复合物的运动之间的偶联在有丝分裂过程中产生力方面起着重要作用。我们目前对这种运动的理解基于许多详细的计算模型。尽管这些模型实现了力转导的可能机制，但它们可以通过改变大量测量参数中的任何一个来扩展，并且没有明确的策略来确定如何在实验中区分它们。在这里，我们试图识别和分析计算模型中存在的两种不同机制。在第一种机制中，解聚 MT 末端的张开原纤维物理上阻止 Dam1 环从末端脱落，而在另一种机制中，一种吸引力将环固定在微管上。基于这种分析，我们讨论了如何区分试图解释 Dam1 环如何留在 MT 上的竞争模型。我们提出了新的实验方法，这些方法可以首次解决这些模型，例如通过改变 Dam1 环的扩散常数（例如，通过将长聚合物与其连接）或通过使用时变负载。
