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 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 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 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 The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model

2019 ◽  
Author(s):  
Duncan C Tourolle né Betts ◽  
Esther Wehrle ◽  
Graeme R Paul ◽  
Gisela A Kuhn ◽  
Patrik Christen ◽  
...  
Keyword(s):  
Healing Process ◽  
Strong Association ◽  
Mechanical Strain ◽  
Mechanical Stimuli ◽  
Tissue Formation ◽  
Micro Computed Tomography ◽  
Element Analysis ◽  
Cross Sectional ◽  
Mechanical Signal

AbstractAn improved understanding of how local mechanical stimuli guide the fracture healing process has the potential to enhance clinical treatment of bone injury. Recent preclinical studies of bone defect in animal models have used cross-sectional data to examine this phenomenon indirectly. In this study, a direct time-lapsed imaging approach was used to investigate the local mechanical strains that precede the formation of mineralised tissue at the tissue scale. The goal was to test two hypotheses: 1) the local mechanical signal that precedes the onset of tissue mineralisation is higher in areas which mineralise, and 2) this local mechanical signal is independent of the magnitude of global mechanical loading of the tissue in the defect. Two groups of mice with femoral defects of length 0.85 mm (n=10) and 1.45 mm (n=9) were studied, allowing for distinct distributions of tissue scale strains in the defects. The regeneration and (re)modelling of mineralised tissue was observed weekly using in vivo micro-computed tomography (micro-CT), which served as a ground truth for resolving areas of mineralised tissue formation. The mechanical environment was determined using micro-finite element analysis (micro-FE) on baseline images. The formation of mineralised tissue showed strong association with areas of higher mechanical strain (area-under-the-curve: 0.91±0.04, true positive rate: 0.85±0.05) while surface based strains could correctly classify 43% of remodelling events. These findings support our hypotheses by showing a direct association between the local mechanical strains and the formation of mineralised tissue.

scholarly journals The Physiology of Mechanoelectrical Transduction Channels in Hearing

2014 ◽  
Vol 94 (3) ◽  
pp. 951-986 ◽  
Author(s):  
Robert Fettiplace ◽  
Kyunghee X. Kim
Keyword(s):  
Hair Cell ◽  
Single Channel ◽  
Single Gene ◽  
Sensorineural Deafness ◽  
Coupled Processes ◽  
Resting Potential ◽  
Mechanical Stimuli ◽  
Open Probability ◽  
Tip Link

Much is known about the mechanotransducer (MT) channels mediating transduction in hair cells of the vertrbrate inner ear. With the use of isolated preparations, it is experimentally feasible to deliver precise mechanical stimuli to individual cells and record the ensuing transducer currents. This approach has shown that small (1–100 nm) deflections of the hair-cell stereociliary bundle are transmitted via interciliary tip links to open MT channels at the tops of the stereocilia. These channels are cation-permeable with a high selectivity for Ca2+; two channels are thought to be localized at the lower end of the tip link, each with a large single-channel conductance that increases from the low- to high-frequency end of the cochlea. Ca2+ influx through open channels regulates their resting open probability, which may contribute to setting the hair cell resting potential in vivo. Ca2+ also controls transducer fast adaptation and force generation by the hair bundle, the two coupled processes increasing in speed from cochlear apex to base. The molecular intricacy of the stereocilary bundle and the transduction apparatus is reflected by the large number of single-gene mutations that are linked to sensorineural deafness, especially those in Usher syndrome. Studies of such mutants have led to the discovery of many of the molecules of the transduction complex, including the tip link and its attachments to the stereociliary core. However, the MT channel protein is still not firmly identified, nor is it known whether the channel is activated by force delivered through accessory proteins or by deformation of the lipid bilayer.

scholarly journals Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel

2020 ◽  
Author(s):  
Lavanya Moparthi ◽  
Peter M. Zygmunt
Keyword(s):  
Ion Channel ◽  
Lipid Bilayers ◽  
Transient Receptor Potential ◽  
Single Channel ◽  
Applied Pressure ◽  
Mechanical Stimuli ◽  
Patch Clamp Technique ◽  
Open Probability ◽  
Pressure Interval

AbstractThe Transient Receptor Potential Ankyrin 1 (TRPA1) channel is an intrinsic chemo- and thermo-sensitive ion channel with distinct sensory signaling properties. Although a role of TRPA1 in mammalian mechanosensory transduction in vivo seems likely, it remains to be shown that TRPA1 has the inherent capability to respond to mechanical stimuli. Here we have used the patch-clamp technique to study the response of human purified TRPA1 (hTRPA1), reconstituted into artificial lipid bilayers, to changes in bilayer pressure. We report that hTRPA1 responded with increased single-channel open probability (Po) within the applied pressure interval of 7.5 to 60 mmHg with a half maximum Po (P50) value of 38.0 ± 2.3 mmHg. The Po value reached a maximum close to 1 (0.87 ± 0.02) at 60 mmHg. Within the same pressure interval, hTRPA1 without its N-terminal ankyrin repeat domain (Δ1-688 hTRPA1) responded fully opened (0.99 ± 0.01) at 60 mmHg and with a P50 value of 39.0 ± 1.1 mmHg. The pressure-evoked responses of hTRPA1 and Δ1-688 hTRPA1 at 45 mmHg were inhibited by the TRPA1 antagonist HC030031, and the activity of purified hTRPA1 at 45 mmHg was abolished by the thiol reducing agent tris(2-carboxyethyl)phosphine (TCEP). In conclusion, hTRPA1 is an inherent mechanosensitive ion channel gated by force-from-lipids. The hTRPA1 mechanosensitivity is dependent on the redox environment, and it is suggested that oxidative stress shifts hTRPA1 into a protein conformation sensitive to mechanical stimuli.

scholarly journals Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Amelia J Thompson ◽  
Eva K Pillai ◽  
Ivan B Dimov ◽  
Sarah K Foster ◽  
Christine E Holt ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Time Lapse ◽  
Time Frame ◽  
Tissue Mechanics ◽  
Tissue Stiffness ◽  
Time Resolved ◽  
Local Tissue ◽  
Close Relationship ◽  
Spatio Temporal

Tissue 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 during development local tissue stiffness changes significantly within tens of minutes. Within this time frame, a stiffness gradient arose in the developing Xenopus brain, and retinal ganglion cell axons turned to follow this gradient. Changes in local tissue stiffness were largely governed by cell proliferation, as perturbation of mitosis diminished both the stiffness gradient and the caudal turn of axons found in control brains. Hence, we identified a close relationship between the dynamics of tissue mechanics and developmental processes, underpinning the importance of time-resolved stiffness measurements.

scholarly journals Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration – an in silico analysis

2021 ◽  
Author(s):  
Camille Perier-Metz ◽  
Georg N. Duda ◽  
Sara Checa
Keyword(s):  
Bone Regeneration ◽  
In Silico ◽  
Volume Fraction ◽  
Computer Modelling ◽  
Mechanical Strain ◽  
In Silico Analysis ◽  
Bone Volume ◽  
Mechanical Stimuli ◽  
Design Strategies ◽  
Scaffold Design

AbstractLarge bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term.

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