Mechanical Stretch Inhibition Sensitizes Proprioceptors to Compressive Stresses

A repetitive gait cycle is an archetypical component within the behavioural repertoire of many if not all
animals including humans. It originates from mechanical feedback within proprioceptors to adjust the
motorprogram during locomotion and thus leads to a periodic orbit in a low dimensional space. Here,
we investigate the mechanics, molecules and neurons responsible for proprioception in Caenorhabditis
(C.) elegans to gain insight into how mechanosensation shapes the orbital trajectory to a well-defined
limit cycle. We used genome editing, force spectroscopy and multiscale modeling and found that
alternating tension and compression with the spectrin network of a single proprioceptor encodes
body posture and informs TRP-4/NOMPC and TWK-16/TREK2 homologs of mechanosensitive
ion channels during locomotion. In contrast to a widely accepted model of proprioceptive ‘stretch’
reception, we found that proprioceptors activated locally under compressive stresses in vivo and in
vitro, and propose that this property leads to compartmentalized activity within long axons delimited
by curvature-dependent mechanical stresses.