The Regulative Role of Neurite Mechanical Tension in Network Development

A bewildering series of dynamical processes take part in the development of the nervous system. Neuron branching dynamics, the continuous formation and elimination of neural interconnections, are instrumental in constructing distinct neuronal networks, which are the functional building blocks of the nervous system. In this study, we investigate and validate the important regulative role of mechanical tension in determining the final morphology of neuronal networks. To single out the mechanical effect, we cultured relatively large invertebrate neurons on clean quartz surfaces. Applied to these surfaces were isolated anchoring sites consisting of carbon nanotube islands to which the cells and the neurites could mechanically attach. Inspection of branching dynamics and network wiring upon development revealed an innate selection mechanism in which one axon branch wins over another. The apparent mechanism entails the build-up of mechanical tension in developing axons. The tension is maintained by the attachment of the growth cone to the substrate or, alternatively, to the neurites of a target neuron. The induced tension promotes the stabilization of one set of axon branches while causing retraction or elimination of axon collaterals. We suggest that these findings represent a crucial, early step that precedes the formation of synapses and regulates neuronal interconnections. Mechanical tension serves as a signal for survival of the axonal branch and perhaps for the subsequent formation of synapses.