[en] Alterations of the axonal morphology are key signatures of traumatic brain injury (TBI). Although the pathobiology of axonal injury has been extensively investigated, the vulnerability of the axonal microcompartment over the soma was still misunderstood. We hypothesized that the soma and the axon of neurons display opposite mechanical behaviors, rendering the axon more sensitive to a mechanical stress. To test this hypothesis, we used a microcontact printing method to control the growth of cortical neuron in a bipolar morphology and the viscoelastic properties of soma and axon microcompartments were measured with magnetic tweezers. Creep experiments showed that neuronal microcompartments exhibit distinct mechanical behaviors: the soma is softer and characterized by an elastic-like behavior, while the neurite is stiffer and viscous-like. By altering cytoskeletal filaments with pharmacological agents, we determined the origin of the compartmentalization of mechanical behaviors within cortical neurons. The nucleus determines the elastic and stress stiffening behavior of the soma, while the sliding of neurofilaments determines the viscous-like state of the neurite. In addition, our results revealed that at the contrary of the soma, the neurite can sense its mechanical environment and becomes softer and more viscous on soft surfaces, showing that, as for the mechanical behavior, the mechanosensitivity is localized to the neuronal microcompartments. Our findings shed light on the importance of the regionalization of neuronal properties to their microcompartments in response to a mechanical insult. Future works will need to investigate the relationship between the mechanical differences of neuronal microcompartments and their functions. In this context, we suggest to consider microprinted neuronal networks as an efficient tool for investigating the effect of the propagation of injury forces on the behavior of neuronal circuits.
