Collaborative Research: Role of Neurofilament Transport in the Growth of Axonal Caliber

神经细胞通过沿着细长的细胞质延伸即轴突传导电信号进行交流。动物已经进化出两种增加轴突传导速度的基本机制。一种是增加轴突直径，另一种是通过称为髓鞘形成的过程来隔离轴突，髓鞘形成的轴突是由髓鞘细胞形成的紧密螺旋包裹的轴突。在脊椎动物中，轴突直径的增长主要是由轴突内被称为神经丝的充满空间的细胞骨架聚合物的积累引起的，这是由髓鞘细胞发出的化学信号局部调节的。众所周知，神经丝是沿着轴突运输的，它们在快速运动和长时间停顿之间交替。神经丝停顿的时间比例可能是它们在轴突中停留时间的主要决定因素。这是一个合作的实验和建模项目，涉及俄亥俄州立大学的生物学家和俄亥俄大学的物理学家。有待检验的中心假设是，髓鞘细胞通过调节神经丝停顿来控制轴突口径。将开发一个计算模型，将神经细丝的移动和停顿行为与它们沿轴突的分布联系起来。该模型将基于实验获得的培养神经元中神经丝运动的详细动力学参数，并将通过组织培养中有髓轴突中神经丝运动的荧光显微镜进行实验验证。拟议的研究将产生一个严格的量化框架，将轴突的大小和形状与其内部成分的运动和停顿行为联系起来，轴突的大小和形状是对其电学特性的关键影响。这项研究将涉及物理和生物科学的研究生和本科生，在计算生物学和实验生物学之间提供综合和跨学科的培训体验。

Nerve cells communicate by conducting electrical signals along slender cytoplasmic extensions known as axons. Animals have evolved two basic mechanisms for increasing axonal conduction velocity. One is to increase axonal diameter and the other is to insulate axons by a process called myelination, which is a tight spiral wrapping of the axons that is formed by myelinating cells. In vertebrates the growth of axon diameter is caused principally by the accumulation of space-filling cytoskeletal polymers called neurofilaments inside the axons, and this is regulated locally by chemical signals from the myelinating cells. It is known that neurofilaments are transported along axons and that they alternate between rapid movements and prolonged pauses. The proportion of the time that the neurofilaments spend pausing is likely to be a principal determinant of their residence time in axons. This is a collaborative experimental and modeling project involving a biologist at Ohio State University and a physicist at Ohio University. The central hypothesis to be tested is that myelinating cells control axonal caliber by regulating neurofilament pausing. A computational model will be developed that relates the moving and pausing behavior of neurofilaments to their distribution along axons. The model will be based on detailed kinetic parameters of neurofilament movement derived experimentally in cultured neurons and will be verified experimentally by fluorescence microscopy of neurofilament movement in myelinated axons in tissue culture. The proposed research will generate a rigorous and quantitative framework that relates the size and shape of axons, which is a key influence on their electrical properties, to the moving and pausing behavior of their internal constituents. The research will involve graduate and undergraduate students in both the physical and biological sciences, providing an integrated and cross-disciplinary training experience at the interface between computational and experimental biology.