Abstract

While our understanding of biochemical cell signaling is increasing rapidly, the current knowledge about cellular responses to physical stimuli is very limited. Local changes in the mechanical properties of a cell’s environment, for example, may provide crucial stimuli particularly during growth and migration. Here we present high-resolution data on the mechanical properties of nerve tissue and cells and show how both neurons and glial cells detect and respond to the stiffness of their substrate. Morphology, growth rate, and fasciculation of outgrowing retinal ganglion cell axons significantly depended on the mechanical properties of their substrate. On softer substrates, retinal ganglion cell axons fasciculated more and preferentially grew in a common direction, similar as in vivo, where these axons build the optic nerve. Glial cells assumed an activated phenotype and spread more on stiffer substrates. We used traction force microscopy and scanning force microscopy in combination with calcium imaging to suggest a possible model for mechanosensing of neurons. Using culture substrates incorporating gradients of mechanical properties we found that CNS cells can even be guided by mechanical stimuli. While neuronal axons were repelled by stiff substrates, activated glial cells were attracted towards them. Thus, cellular mechanosensitivity could not only be involved in developmental processes in the CNS such as neuronal guidance, but also in pathological processes such as foreign body reactions to stiff neural implants. The mechanical mismatch between implant and tissue could cause the repulsion of neurons and at the same time the attraction of glial cells, thus leading to the implant’s encapsulation by reactive glial cells. Exploiting this knowledge may ultimately lead to the development of a new generation of neural implants, incorporating appropriate mechanical cues which support healthy tissue structure.