Abstract：
Mechanical stress significantly affects the physiological functions of cells, including tissue homeostasis, cytoskeletal alterations, and intracellular transport. As a major cytoskeletal component, microtubules respond to mechanical stimulation by altering their alignment and polymerization dynamics. Previously, we reported that microtubules may modulate cargo transport by one of the microtubule-associated motor proteins, dynein, under compressive mechanical stress. Despite the critical role of tensile stress in many biological functions, how tensile stress on microtubules regulates cargo transport is yet to be unveiled. The present study demonstrates that the low-level tensile stress-induced microtubule deformation facilitates dynein-driven transport. We validate our experimental findings using all-atom molecular dynamics simulation. Our study may provide important implications for developing new therapies for diseases that involve impaired intracellular transport.
摘要：
机械应力显著影响细胞的生理功能,包括组织稳态，细胞骨架改变，和细胞内运输。作为主要的细胞骨架成分，微管通过改变其排列和聚合动力学来响应机械刺激。以前,我们报道了微管可能通过一种微管相关的运动蛋白调节货物运输，动力蛋白,在压缩机械应力下。尽管拉伸应力在许多生物学功能中起着关键作用，微管上的拉伸应力如何调节货物运输尚未公布。本研究表明，低水平的拉伸应力诱导的微管变形促进了动力蛋白驱动的运输。我们使用全原子分子动力学模拟验证了我们的实验结果。我们的研究可能为开发涉及细胞内运输受损的疾病的新疗法提供重要意义。
