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.
