Mechanical Control of the Sense of Touch by β Spectrin

The ability to sense and respond to mechanical stimuli emanates from sensory neurons and is shared by most, if not all animals. Exactly how such neurons receive and distribute mechanical signals during touch sensation remains mysterious. Here, we show that sensation of mechanical forces depends on a continuous, pre-stressed spectrin cytoskeleton inside neurons. Mutations in the tetramerization domain of C. elegans β-spectrin (UNC-70), an actin-membrane cross-linker, cause defects in sensory neuron morphology under compressive stress in moving animals. Through AFM force spectroscopy experiments on isolated neurons, in vivo laser axotomy and FRET imaging to measure force across single cells and molecules, we show that spectrin is held under constitutive tension in living animals, which contributes to an elevated pre-stress in touch receptor neurons. Genetic manipulations that decrease such spectrin-dependent tension also selectively impair touch sensation, suggesting that such pretension is essential for efficient responses to external mechanical stimuli.