SGER: The Effects of Mechanical Foreces on Neural Growth Rates

环境提供了广泛的线索，生长和再生的神经细胞需要成功地达到他们的目标。为了识别这些线索和了解神经元的生长和寻路，人们已经采取了各种方法。所有这些方法都仔细地控制了神经元环境的特定成分，如生化因素、与其他细胞的相互作用或局部电场。然而，施加在神经元上的物理力是细胞环境的一个组成部分，还没有作为潜在的生长调节因素进行研究。这项研究的目的是调查机械环境影响神经生长速度和方向的能力。人体内的细胞不断地受到机械力的作用，这些输入在早期胚胎发育和后来充分发育的组织的重塑期间诱导反应。对机械环境的敏感性是许多类型细胞的特征。肌肉、骨、软骨、内皮细胞和成纤维细胞在受到物理力量的作用时，都表现出生长或形态的改变。神经细胞通常不被认为是机械反应的；然而，有限数量的研究证明了对机械刺激的可逆反应，这些研究形成了机械刺激可能指导和促进生长的假设的基础。本研究将探讨机械刺激对培养感觉神经节神经元生长和定向的影响。在控制条件下，这些培养物的生长速度和特征得到了很好的表征，生长速度将通过机械刺激和非刺激细胞的延时视频显微镜记录来测量。由于细胞对机械力的反应通常取决于施加的方法，这些研究中的机械力将通过将细胞放置在能够对神经元施加压缩、拉伸或剪切的三种加载装置中的一种来施加。在生长速度或方向上的任何优先反应都将与每个实验所使用的载荷的大小和类型相关。这里提出的实验的最终目的是确定机械力是否能够指导或调节神经突起的生长。这一结果将对我们理解控制轴突生长的过程产生相当大的影响。

The environment provides a wide range of cues that growing and regenerating nerve cells need to successfully reach their targets. A variety of approaches have been pursued to identify these cues and to understand neuronal growth and pathfinding. All of these methods have carefully controlled a particular component of the neuron's environment such as biochemical factors, interactions with other cells, or local electric fields. However, the amount of physical force that is exerted on neurons is one component of the cell environment which has not been investigated as a potential growth regulator. It is the objective of this research to investigate the ability of the mechanical environment to affect neural growth rates and directions. Cells within the body are subjected to mechanical forces on a continuous basis, and these inputs induce responses during early embryonic development and later remodeling of fully developed tissues. Sensitivity to the mechanical environment is a characteristic of many types of cells. Muscle, bone, cartilage, endothelial and fibroblast cells all exhibit modified growth or morphology when subjected to physical forces. Nerve cells are not typically thought of mechano-responsive; however a limited number of studies have demonstrated reversible responses to mechanical stimulation and these investigations form the basis for the hypothesis that mechanical stimulation may direct and increase growth. This research will explore the ability of mechanical stimulation to affect the growth and orientation of cultured sensory ganglion neurons. The growth rates and characteristics of these cultures have been well characterized under control conditions, and outgrowth rates will be measured from time-lapse video microscopy recordings of both mechanically stimulated and non-stimulated cells. Since the response of cells to mechanical forces is often dependent on the method of application, the mechanical forces in these studies will be applied to the cells by placing them in one of three lo ading apparatus that will be capable of applying either compression, elongation, or shear to the neurons. Any preferential response in outgrowth rates or directions will be correlated with the magnitude and type of loading used for each experiment. The ultimate aim of the experiments proposed here is to determine whether mechanical forces can act to direct or modulate neurite outgrowth. The results will have considerable impact on our understanding of the processes controlling neurite outgrowth.