力学信号对神经元的生长形貌和兴奋传递等方面具有重要作用。动作电位产生的动力学过程涉及力学和电生理学的耦合调控,也是神经生物力学领域中一个富有挑战性的课题。此外,轴突张力已被证明在神经寻路和延伸过程中发挥关键作用。因此,对轴突本征张力和力学性质的实验表征具有重要的理论意义。本文以神经元为研究对象,结合理论建模、数值计算和实验,对神经元兴奋的多物理场耦合机制和轴突张力和力学性质表征进行探究。 首先,建立了描述神经元兴奋产生的力电耦合模型。基于Helfrich弹性膜理论和Hodgkin-Huxley模型,给出了动作电位期间神经元胞体形状和电压控制方程,并在轴对称条件下发展相应的算法进行求解。数值解能够较好的解释相关实验中观察到的现象。进一步研究表明,神经元力学参数会显著影响动作电位的产生时间和幅值,并给出了力学信号调控电生理活性的离子机制。此外,神经元兴奋对膜形貌演化的研究结果表明,伴随膜电压升高,神经元胞体会产生球化现象,胞体的顶点膜曲率在去极化阶段呈先增大后减小的趋势。 其次,建立了一套高分辨率表征神经元轴突张力和力学性质的非接触实验方法。以小鼠的海马神经元为研究对象,通过统计轴突激光烧蚀后回缩的实验结果并发展了相应的本构模型,反演得到轴突生理状态下的张力和力学参数。在神经元原代培养中,研究了基底刚度对神经元生长状态的影响。 最后,基于上述建立的非接触表征方法,研究了神经元轴突张力与其直径的相关性。结果显示,随着轴突直径增大,张力呈指数增长。这揭示了不同生长状态下轴突主动保持的张力水平。随后引入轴突的粘性模型,在亚细胞尺度上研究了轴突的粘性性质,得到海马神经元马达蛋白的平均粘附时间。此外,研究了基底刚度和切割位置对神经元轴突张力和力学性质的影响。发现基底刚度会显著影响轴突的张力水平和阻尼系数。同时,轴突不同位置处的张力水平也不同,前端的张力值更大,这与轴突的生长动力学理论一致。这些研究将为深入认识神经系统的发育与电活性提供重要的参考价值。
Mechanical signals play an important role in neuronal growth, morphology, and excitation transmission. The dynamic process of action potential generation involves coupled regulation of mechanics and electrophysiology, which is also a challenging topic in the field of neural biomechanics. Furthermore, axonal tension has been shown to play a key role in neural pathfinding and extension processes. Therefore, the experimental characterization of the intrinsic tension and mechanical properties of axons is of great theoretical significance. In this thesis, taking neurons as the research object, combining theoretical modeling, numerical calculation and experiments, the multi-physics coupling mechanism of neural excitation and the characterization of axonal tension and mechanical properties were explored.First, an electromechanical coupling model describing the excitation generation of neurons is developed. Based on the Helfrich elastic membrane theory and the Hodgkin–Huxley model, the neuronal cell body shape and voltage control equations during action potentials are given. And the corresponding algorithm is developed for solving under axisymmetric conditions, and the numerical solution can better explain the phenomena observed in the relevant experiments. Further studies have showed that neuronal mechanical parameters significantly affect the timing and amplitude of action potential generation, and the ionic mechanism for the regulation of electrophysiological activity by mechanical signals has been given. In addition, the results of the study on the evolution of membrane morphology by neuronal excitation show that, along with the increase of membrane voltage, the neuronal cytosol produces spherification and the vertex membrane curvature of the cytosol tends to increase and then decrease during the depolarization phase.Second, a set of non–contact experimental methods for high–resolution characterization of axonal tension and mechanical properties of neurons is developed. Using mouse hippocampal neurons as the research object, the corresponding axonal intrinsic tension and mechanical properties of axons are obtained by inversion of the experimental structure of axons retracted after laser ablation to develop a corresponding axonal intrinsic structure model. The effect of basal stiffness on the growth state of neurons is investigated in primary neuronal cultures.Finally, based on the non–contact characterization method established above, the correlation between neuronal axonal tension and its diameter is investigated. The results on line show an exponential increase in tension with increasing axon diameter. This reveals the level of tension actively maintained by axons in different growth states. Subsequently, the adhesion model of axons is introduced, and the adhesion properties of axons are studied at the subcellular scale to obtain the mean adhesion time of motor proteins in hippocampal neurons. Additionally, the effects of basal stiffness and cutting position on the axonal tension and mechanical properties of neuronal axons are investigated. The basal stiffness is found to significantly affect the axonal tension level and damping coefficient. Also, the tension levels at different locations of the axon differed, with greater tension values at the anterior end, which is consistent with the dynamic theory of axon growth. These studies will provide important reference values for an in-depth understanding of the development and electrical activity of the nervous system.