title: 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.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Amy L
authors.initials: AL
authors.lastname: Eastwood
authors.affiliation: Department of Physics, University of California, San Diego, CA 92093; Department of Physics and Istituto Nazionale di Fisica Nucleare (INFN), University of Milano, 20133 Milan, Italy;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sanzeni
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Petzold
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Physics, University of California, San Diego, CA 92093;
authors.forename: Massimo
authors.initials: M
authors.lastname: Vergassola
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Pruitt
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305; mbgoodman@stanford.edu.
authors.forename: Miriam B
authors.identifier: http://orcid.org/0000-0002-5810-1272
authors.initials: MB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D008322:Mammals / Q000502:physiology; D040542:Mechanotransduction, Cellular; D010812:Physical Stimulation; D014110:Touch
keywords: MEMS-based tools; cellular electrophysiology; mechanobiology; mechanosensitive ion channels; somatosensation