An asymmetric mechanical code ciphers curvature-dependent proprioceptor activity

Abstract

A repetitive gait cycle is an archetypical component within the behavioral repertoire of many animals including humans. It originates from mechanical feedback within proprioceptors to adjust the motor program 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 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 curvaturedependent mechanical stresses.

Axonal plasticity in response to active forces generated through magnetic nano-pulling

“…The isolation of primary C. elegans neurons was performed following a previously described method. 106 Briefly, after synchronization, worms were seeded onto peptone-enriched plates and incubated at room temperature (RT). Once populated with eggs, the plates were washed with Milli-Q H 2 O and the eggs collected.…”

FLInt: Single Shot Safe Harbor Transgene Integration viaFluorescentLandmarkInterference

“…On the last day of developmental assessment, the adult animals were placed on the new plate and the moving trace on bacterial lawn captured. The locomotion behavior was observed under the lab-built microscope (WormTracker (Das et al . 2021)).…”

“…Furthermore, extrachromosomal arrays contain large copy numbers of the injected DNA, which often causes overexpression artefacts, but have the advantage that transgenes become visible even beyond their native levels. For example, many fluorescent tags to endogenous proteins are poorly visible due to their low expression levels and promoter activity (Das et al 2021; Walker et al 2000). The problem of unstable inheritance can be mitigated by integrating the transgenic array.…”

“…2022). Recently, Frokjaer-Jensen and colleagues generated a library containing 147 strains carrying single-copy loci expressing the red fluorophore tdTomato in somatic nu-clei, in addition to 142 nuclearly localized GFP strains (Frøkjær-Jensen et al 2014), which have aided mapping and in genetic experiments (Das et al 2021; Fay 2006; LaBella et al 2020; Noble et al 2020). Originally, these strains were generated as dom-inant genetic markers and can also be used as landmarks to map genetic position of mutants and transgenes.…”

Recent Advances of Optical Tweezers–Based Dynamic Force Spectroscopy and Mechanical Measurement Assays for Live-Cell Mechanobiology

“…Notably, Feng et al further demonstrated that, in the absence of force, the initial TCR calcium triggering requires much higher pMHC ligand density-690 folds higher than physiologically observed [38]. Moreover, Das et al performed OT-DFS to pull membrane tethers from Caenorhabditis elegans DAV neurons with the positive and the negative tension gradient [37]. They observed that the subsequential calcium mobilization upon increased membrane tension was associated with the activation of the TRP-4 channel and nompC (no mechanoreceptor potential C), which consequentially confines the neuronal activity for movement.…”