Department of Applied Physics, Graduate School of Engineering, Tohoku University, Sendai, Japan.
Department of Applied Physics, Graduate School of Engineering, Tohoku University, Sendai, Japan.
Biophys J. 2021 May 4;120(9):1605-1614. doi: 10.1016/j.bpj.2021.02.018. Epub 2021 Feb 20.
Synaptic cargo transport by kinesin and dynein in hippocampal neurons was investigated by noninvasively measuring the transport force based on nonequilibrium statistical mechanics. Although direct physical measurements such as force measurement using optical tweezers are difficult in an intracellular environment, the noninvasive estimations enabled enumerating force-producing units (FPUs) carrying a cargo comprising the motor proteins generating force. The number of FPUs served as a barometer for stable and long-distance transport by multiple motors, which was then used to quantify the extent of damage to axonal transport by dynarrestin, a dynein inhibitor. We found that dynarrestin decreased the FPU for retrograde transport more than for anterograde transport. This result indicates the applicability of the noninvasive force measurements. In the future, these measurements may be used to quantify damage to axonal transport resulting from neuronal diseases, including Alzheimer's, Parkinson's, and Huntington's diseases.
应用非平衡统计力学方法，通过非侵入性测量运输力，研究了海马神经元中驱动蛋白和动力蛋白介导的突触货物运输。虽然在细胞内环境中，使用光镊等直接物理测量方法较为困难，但这种非侵入性的估计方法能够对产生力的包含马达蛋白的货物的力产生单元（FPUs）进行计数。FPUs 的数量可以作为多个马达稳定长距离运输的晴雨表，然后用于量化dynarrestin（一种动力蛋白抑制剂）对轴突运输的破坏程度。我们发现 dynarrestin 对逆行运输的 FPU 影响大于对顺行运输的影响。这一结果表明了非侵入性力测量的适用性。将来，这些测量方法可能用于量化包括阿尔茨海默病、帕金森病和亨廷顿病在内的神经疾病导致的轴突运输损伤。
