Neuron Sub-Compartments Exhibit Opposite Rheological and Mechanosensitive Properties

Abstract

Although a mechanical insult is the initiating factor in brain injuries, the response of neurons to mechanical loads remains largely elusive. This gap in our knowledge probably exists because most of the investigations were conducted at the organ or tissue levels without considering the structural specificity of the CNS at the cellular level. In this context, the first step towards a distinction between gray and white matters pathologies is therefore the separate evaluation of the mechanical properties of the two main subcellular compartments of neurons: the soma (i.e., a cell body ) and the processes (i.e., axons and neurites). To answer this question, we have performed creeping experiments at the subcellular level with magnetic tweezers to determine the rheological behavior of soma and neurite compartments of individual cortical neurons. Our results clearly indicate two opposite mechanical responses with a soft cell body characterized by a solid-like behavior and a stiffer neurite compartment described by a viscous-like behavior. By using selective pharmacological agents, we have assessed the individual role of cytoskeletal filaments and associated molecular motors in the mechanical behavior of both neuron subcompartments. We have determined that the nucleus is reponsible of the soma mechanical properties, whereas microtubules and neurofilaments are associated to the elastic and viscous contributions of the neurite mechanics, respectively. We have next investigated whether neuron sub-compartments are sensitive to stiffness modifications of their surrounding, as observed during scar formation. We found that neuron cell body is insensitive to changes in matrix stiffness, whereas the neurite compartment changes its stiffness and exhibits a pronounced viscous state on soft matrices. On the basis of these findings, we propose a simple mechanical model that provides a conceptual framework for the rheological and mechanosensitive behaviors of cortical neurons at the subcellular level.