Tissue mechanics govern the rapidly adapting and symmetrical response to touch

Abstract

Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.

Activation of the Caenorhabditis elegans Degenerin Channel by Shear Stress Requires the MEC-10 Subunit

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Tunable molecular tension sensors reveal extension-based control of vinculin loading

“…Through these improvements, which included a switch to the Intracellularly, gradients in vinculin tension have been reported in cells adhered to micropost arrays, 276 although tension asymmetries were mainly attributed to the presence of the discontinuous substrates 277 (Sarangi et al, 2017). We show that these asymmetric molecular loads, high at the distal tips and low at (Saez et al, 2005) and that strain determines the activation of touch-sensitive channels in in 288 vivo models (Eastwood et al, 2015). However, while vinculin appears to be under extension-control in…”

The Tactile Receptive Fields of Freely Moving Caenorhabditis elegans Nematodes

“…Given that the anterior and posterior TRNs detect forces in the nano-Newton to micro-Newton range 35,36 , we delivered force pulses with values between 50 nN and 10,000 nN. We measured forceresponse curves at three anterior body positions (25%, 35%, and 45% of the distance from the head), and two posterior positions (55% and 75% of the distance from the head).…”