scholarly journals Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans

2019 ◽  
Author(s):  
S. Katta ◽  
A. Sanzeni ◽  
A. Das ◽  
M. Vergassola ◽  
M.B. Goodman
Keyword(s):  
Temporal Dynamics ◽  
Mechanical Strain ◽  
Tissue Mechanics ◽  
Mechanical Stimuli ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
C Elegans ◽  
Somatosensory Neurons ◽  
Touch Response

AbstractTouch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged C. elegans’ touch receptor neurons (TRNs) as a simple model amenable to in vivo whole-cell patch clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics that we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.SummaryThrough experiment and simulation, Katta et al. reveal that pushing faster and deeper recruits more and more distant mechano-electrical transduction channels during touch. The net result is a dynamic receptive field whose size and shape depends on tissue mechanics, stimulus parameters, and channel distribution within sensory neurons.

scholarly journals Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans

2019 ◽  
Vol 151 (10) ◽  
pp. 1213-1230 ◽  
Author(s):  
Samata Katta ◽  
Alessandro Sanzeni ◽  
Alakananda Das ◽  
Massimo Vergassola ◽  
Miriam B. Goodman
Keyword(s):  
Temporal Dynamics ◽  
Mechanical Strain ◽  
Response Strength ◽  
Tissue Mechanics ◽  
Mechanical Stimuli ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
Somatosensory Neurons ◽  
Touch Response

Touch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged Caenorhabditis elegans’ touch receptor neurons as a simple model amenable to in vivo whole-cell patch-clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.

scholarly journals Touch-induced mechanical strain in somatosensory neurons is independent of extracellular matrix mutations in Caenorhabditis elegans

2020 ◽  
Vol 31 (16) ◽  
pp. 1735-1743 ◽  
Author(s):  
Adam L. Nekimken ◽  
Beth L. Pruitt ◽  
Miriam B. Goodman
Keyword(s):  
Extracellular Matrix ◽  
Caenorhabditis Elegans ◽  
Mechanical Strain ◽  
Tissue Mechanics ◽  
Touch Receptor Neurons ◽  
Somatosensory Neurons ◽  
Receptor Neurons ◽  
Bulk Tissue

We visualized and measured touch-induced mechanical strain in somatosensory neurons in vivo and found that mutations affecting links between the extracellular matrix and the touch receptor neurons had little effect on strain transmission. The findings suggest that bulk tissue mechanics play an important role in transmitting the energy carried in a touch.

scholarly journals Simultaneous in vivo time-lapse stiffness mapping and fluorescence imaging of developing tissue

2018 ◽  
Author(s):  
Amelia J. Thompson ◽  
Iva K. Pillai ◽  
Ivan B. Dimov ◽  
Christine E. Holt ◽  
Kristian Franze
Keyword(s):  
Fluorescence Imaging ◽  
Temporal Dynamics ◽  
Time Lapse ◽  
Tissue Mechanics ◽  
Tissue Stiffness ◽  
Time Resolved ◽  
Force Microscopy ◽  
Atomic Force ◽  
Spatio Temporal

AbstractTissue mechanics is important for development; however, the spatio-temporal dynamics of in vivo tissue stiffness is still poorly understood. We here developed tiv-AFM, combining time-lapse in vivo atomic force microscopy with upright fluorescence imaging of embryonic tissue, to show that in the developing Xenopus brain, a stiffness gradient evolves over time because of differential cell proliferation. Subsequently, axons turn to follow this gradient, underpinning the importance of time-resolved mechanics measurements.

scholarly journals Touch-induced Mechanical Strain in Somatosensory Neurons is Independent of Extracellular Matrix Mutations in C. elegans

2019 ◽  
Author(s):  
Adam L. Nekimken ◽  
Beth L. Pruitt ◽  
Miriam B. Goodman
Keyword(s):  
Extracellular Matrix ◽  
Fluorescent Protein ◽  
Mechanical Strain ◽  
C Elegans ◽  
Mechanosensory Neurons ◽  
State Touch ◽  
Touch Receptor Neurons ◽  
Somatosensory Neurons ◽  
Measured Strain ◽  
Receptor Neurons

AbstractCutaneous mechanosensory neurons are activated by mechanical loads applied to the skin, and these stimuli are proposed to generate mechanical strain within sensory neurons. Using a microfluidic device to deliver controlled stimuli to intact animals and large, immobile, and fluorescent protein-tagged mitochondria as fiducial markers in the touch receptor neurons (TRNs), we visualized and measured touch-induced mechanical strain in C. elegans worms. At steady-state, touch stimuli sufficient to activate TRNs induce an average strain of 3.1% at the center of the actuator and this strain decays to near zero at the edges of the actuator. We also measured strain in animals carrying mutations affecting links between the extracellular matrix (ECM) and the TRNs but could not detect any differences in touch-induced mechanical strain between wild-type and mutant animals. Collectively, these results demonstrate that touching the skin induces local mechanical strain in intact animals and suggest that a fully intact ECM is not essential for transmitting mechanical strain from the skin to cutaneous mechanosensory neurons.

scholarly journals Salmonella biofilms program innate immunity for persistence in Caenorhabditis elegans

2019 ◽  
Vol 116 (25) ◽  
pp. 12462-12467 ◽  
Author(s):  
Stuti K. Desai ◽  
Anup Padmanabhan ◽  
Sharvari Harshe ◽  
Ronen Zaidel-Bar ◽  
Linda J. Kenney
Keyword(s):  
Caenorhabditis Elegans ◽  
Temporal Dynamics ◽  
Innate Immune ◽  
Heterologous Host ◽  
C Elegans ◽  
Parasitic Lifestyle ◽  
Induced Changes ◽  
Infectious Form

The adaptive in vivo mechanisms underlying the switch in Salmonella enterica lifestyles from the infectious form to a dormant form remain unknown. We employed Caenorhabditis elegans as a heterologous host to understand the temporal dynamics of Salmonella pathogenesis and to identify its lifestyle form in vivo. We discovered that Salmonella exists as sessile aggregates, or in vivo biofilms, in the persistently infected C. elegans gut. In the absence of in vivo biofilms, Salmonella killed the host more rapidly by actively inhibiting innate immune pathways. Regulatory cross-talk between two major Salmonella pathogenicity islands, SPI-1 and SPI-2, was responsible for biofilm-induced changes in host physiology during persistent infection. Thus, biofilm formation is a survival strategy in long-term infections, as prolonging host survival is beneficial for the parasitic lifestyle.

scholarly journals Tissue mechanics govern the rapidly adapting and symmetrical response to touch

2015 ◽  
Vol 112 (50) ◽  
pp. E6955-E6963 ◽  
Author(s):  
Amy L. Eastwood ◽  
Alessandro Sanzeni ◽  
Bryan C. Petzold ◽  
Sung-Jin Park ◽  
Massimo Vergassola ◽  
...  
Keyword(s):  
Mechanical Energy ◽  
Physical World ◽  
Tissue Mechanics ◽  
Applied Force ◽  
General Mechanism ◽  
Channel Activation ◽  
Mechanoelectrical Transduction ◽  
Mechanical Filter ◽  
Somatosensory Neurons

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.

scholarly journals Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans.

1996 ◽  
Vol 133 (5) ◽  
pp. 1071-1081 ◽  
Author(s):  
C C Lai ◽  
K Hong ◽  
M Kinnell ◽  
M Chalfie ◽  
M Driscoll
Keyword(s):  
Caenorhabditis Elegans ◽  
Ion Channel ◽  
Critical Role ◽  
Comparative Sequence Analysis ◽  
Mechanical Stimuli ◽  
Transmembrane Topology ◽  
C Elegans ◽  
Carboxy Terminal

The process by which mechanical stimuli are converted into cellular responses is poorly understood, in part because key molecules in this mode of signal transduction, the mechanically gated ion channels, have eluded cloning efforts. The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechanosensitive ion channel that plays a critical role in touch reception. Comparative sequence analysis of C. elegans and Caenorhabditis briggsae mec-4 genes was used to initiate molecular studies that establish MEC-4 as a 768-amino acid protein that includes two hydrophobic domains theoretically capable of spanning a lipid bilayer. Immunoprecipitation of in vitro translated mec-4 protein with domain-specific anti-MEC-4 antibodies and in vivo characterization of a series of mec-4lacZ fusion proteins both support the hypothesis that MEC-4 crosses the membrane twice. The MEC-4 amino- and carboxy-terminal domains are situated in the cytoplasm and a large domain, which includes three Cys-rich regions, is extracellular. Definition of transmembrane topology defines regions that might interact with the extracellular matrix or cytoskeleton to mediate mechanical signaling.

scholarly journals Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device

2017 ◽  
Author(s):  
Patrick D. McClanahan ◽  
Joyce H. Xu ◽  
Christopher Fang-Yen
Keyword(s):  
Caenorhabditis Elegans ◽  
Microfluidic Device ◽  
Receptive Fields ◽  
The Body ◽  
Mechanical Stimuli ◽  
C Elegans ◽  
Response Characteristics ◽  
Touch Receptor Neurons ◽  
Touch Response ◽  
Receptor Neurons

AbstractThe roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms. We used this assay to characterize the behavioral responses to gentle touch stimuli and the less well studied harsh (nociceptive) touch stimuli. First, we measured the relative response thresholds of gentle and harsh touch. Next, we quantified differences in the receptive fields between wild type worms and a mutant with non-functioning posterior touch receptor neurons. We showed that under gentle touch the receptive field of the anterior touch receptor neurons extends into the posterior half of the body. Finally, we found that the behavioral response to gentle touch does not depend on the locomotion of the animal immediately prior to the stimulus, but does depend on the location of the previous touch. Responses to harsh touch, on the other hand, did not depend on either previous velocity or stimulus location. Differences in gentle and harsh touch response characteristics may reflect the different innervation of the respective mechanosensory cells. Our assay will facilitate studies of mechanosensation, sensory adaptation, and nociception.

scholarly journals Automated and controlled mechanical stimulation and functional imaging in vivo in C. elegans

Lab on a Chip ◽  
2017 ◽  
Vol 17 (15) ◽  
pp. 2609-2618 ◽  
Author(s):  
Yongmin Cho ◽  
Daniel A. Porto ◽  
Hyundoo Hwang ◽  
Laura J. Grundy ◽  
William R. Schafer ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Mechanical Stimulation ◽  
Mechanical Stimuli ◽  
Microfluidic Platform ◽  
C Elegans ◽  
Neural Imaging ◽  
Wide Range

A new automated microfluidic platform can deliver a wide range of mechanical stimuli for functional neural imaging inC. elegans.

scholarly journals Tissue mechanics and somatosensory neural responses govern touch sensation inC. elegans

2018 ◽  
Author(s):  
A. Sanzeni ◽  
S. Katta ◽  
B.C. Petzold ◽  
B.L. Pruitt ◽  
M.B. Goodman ◽  
...  
Keyword(s):  
Model Organism ◽  
Quantitative Model ◽  
Tissue Mechanics ◽  
The Body ◽  
Elastic Model ◽  
Prime Model ◽  
Neural Responses ◽  
C Elegans ◽  
Somatosensory Neurons ◽  
Broad Variety

The sense of touch hinges on tissues transducing stimuli applied to the skin and somatosensory neurons converting mechanical inputs into currents. Like mammalian Pacinian corpuscles, the light-touch response of the prime model organismC. elegansadapts rapidly, and is symmetrically activated by the onset and offset of a step indentation. Here, we propose a quantitative model that combines transduction of stimuli across the skin and subsequent gating of mechanoelectrical channels. For mechanics, we use an elastic model based on geometrically-nonlinear deformations of a pressurized cylindrical shell. For gating, we build upon consequences of the dermal layer’s thinness and tangential stimuli. Our model demonstrates how the onset-offset symmetry arises from the coupling of mechanics and adaptation, and accounts for experimental neural responses to a broad variety of stimuli. Predicted effects of modifications in the mechanics or the internal pressure of the body are tested against mechanical and neurophysiological experiments.

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