Glial cell mechanosensitivity is reversed by adhesion cues

Brain tissues demonstrate heterogeneous mechanical properties, which evolve with aging and pathologies. The observation in these tissues of smooth to sharp rigidity gradients raises the question of brain cells responses to both different values of rigidity and their spatial variations. Here, we use recent techniques of hydrogel photopolymerization to achieve stiffness structuration down to micrometer resolution. We investigate primary neuron adhesion and orientation as well as glial cell adhesive and proliferative properties on multi-rigidity polyacrylamide hydrogels presenting a uniform density of adhesive molecules. We first observed that neurons grow following rigidity gradients. Then, our main observation is that glial cell adhesion and proliferation can be enhanced on stiff or on soft regions depending on the adhesive coating of the hydrogel, i. e. fibronectin or poly-L-lysine/laminin. This behavior was unchanged in the presence or not of neuronal cells. In addition, and contrarily to other cell types, glial cells were not confined by sharp, micron-scaled gradients of rigidity. Our observations suggest that their mechanosensitivity could involve adheison-related mechanosensitive pathways that are specific to brain tissues