The enteric nervous system is 10 times stiffer than the brain.

Neural tissues of the central nervous system are among the softest and most fragile in the human body, protected from mechanical perturbation by the skull and the spine. In contrast, the enteric nervous system is embedded in a compliant, contractile tissue and subject to chronic, high-magnitude mechanical stress. Do neurons and glia of the enteric nervous system display specific mechanical properties to withstand these forces? Using nano-indentation combined with immunohistochemistry and second harmonic generation imaging of collagen, we discovered that enteric ganglia in adult mice are an order of magnitude more resistant to deformation than brain tissue. We found that glia-rich regions in ganglia have a similar stiffness to neuron-rich regions and to the surrounding smooth muscle: ∼3 kPa at a 3 μm indentation depth and ∼7 kPa at an 8 μm depth. Differences in the adhesion strength of the different tissue layers to the glass indenter were scarce. The collagen shell surrounding ganglia and inter-ganglionic fibers may play a key role in strengthening the enteric nervous system to resist the manifold mechanical challenges it faces.