美国约翰霍普金斯大学Shigeki Watanabe等研究人员合作发现，膜力学决定轴突珍珠串形态和功能。这一研究成果于2024年12月2日在线发表在国际学术期刊《自然—神经科学》上。

研究人员展示了，小鼠中枢神经系统的无髓鞘轴突在其长度上重复分布着，约200纳米直径的非突触性纳米小膨大部位，间隔着约60纳米直径的细长缆线，形态类似珍珠串。计算机模拟表明，这种轴突纳米珍珠状形态可以通过膜的机械性质来解释。

通过干扰膜性质的处理，如高渗或低渗溶液、去除胆固醇和非肌肉型肌动蛋白II抑制，都会改变轴突的纳米珍珠状形态，从而确认了膜力学在决定轴突形态中的作用。

此外，神经元活动调节细胞膜上的胆固醇浓度，导致轴突纳米珍珠的变化，并使得动作电位传导速度减慢。

这些数据揭示了生物物理力在决定轴突形态和功能中的作用，并且膜力学的调节可能是无髓鞘轴突可塑性的基础。

据了解，轴突是超薄的膜状电缆，专门用于传导动作电位。尽管它们的直径沿长度变化，但其形态是如何确定的仍不清楚。

附：英文原文

Title: Membrane mechanics dictate axonal pearls-on-a-string morphology and function

Author: Griswold, Jacqueline M., Bonilla-Quintana, Mayte, Pepper, Renee, Lee, Christopher T., Raychaudhuri, Sumana, Ma, Siyi, Gan, Quan, Syed, Sarah, Zhu, Cuncheng, Bell, Miriam, Suga, Mitsuo, Yamaguchi, Yuuki, Chreau, Ronan, Valentin Ngerl, U., Knott, Graham, Rangamani, Padmini, Watanabe, Shigeki

Issue&Volume: 2024-12-02

Abstract: Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200nm in diameter repeatedly along their length interspersed with a thin cable ~60nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.

DOI: 10.1038/s41593-024-01813-1

Source: https://www.nature.com/articles/s41593-024-01813-1