scholarly journals Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
M Rocio Servin-Vences ◽  
Mirko Moroni ◽  
Gary R Lewin ◽  
Kate Poole
Keyword(s):  
High Speed ◽  
Direct Evidence ◽  
Mechanical Stimuli ◽  
Functional Importance ◽  
Mechanical Loads ◽  
Mechanoelectrical Transduction ◽  
Cartilage Homeostasis ◽  
Cell Substrate ◽  
Pillar Arrays ◽  
Current Activation

The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively. Both TRPV4 and PIEZO1 channels contribute to currents activated by stimuli applied at cell-substrate contacts but only PIEZO1 mediates stretch-activated currents. These data demonstrate that there are separate, but overlapping, mechanoelectrical transduction pathways in chondrocytes.

High Fidelity Computational Model of Bone Remodeling Cellular Mechanisms

2010 ◽  
Author(s):  
Charles L. Penninger ◽  
Andrés Tovar ◽  
Glen L. Niebur ◽  
John E. Renaud
Keyword(s):  
Bone Remodeling ◽  
Computational Models ◽  
Bone Adaptation ◽  
Daily Activities ◽  
High Fidelity ◽  
Mechanical Stimuli ◽  
Cellular Activity ◽  
Cellular Mechanisms ◽  
Mechanical Loads ◽  
Metabolic Activities

One of the most intriguing aspects of bone is its ability to grow, repair damage, adapt to mechanical loads, and maintain mineral homeostasis [1]. It is generally accepted that bone adaptation occurs in response to the mechanical demands of our daily activities; moreover, strain and microdamage have been implicated as potential stimuli that regulate bone remodeling [2]. Computational models have been used to simulate remodeling in an attempt to better understand the metabolic activities which possess the key information of how this process is carried out [3]. At present, the connection between the cellular activity of remodeling and the applied mechanical stimuli is not fully understood. Only a few mathematical models have been formulated to characterize the remolding process in terms of the cellular mechanisms that occur [4,5].

Local Shear Deformation in Whole Cartilage Explants Determined by Texture Correlation

2011 ◽  
Author(s):  
Jonathan T. Henderson ◽  
Garrett Shannon ◽  
Kai Yuen ◽  
Corey P. Neu
Keyword(s):  
The United States ◽  
Cartilage Explants ◽  
Mechanical Stimuli ◽  
Cartilage Homeostasis ◽  
Cellular Mechanotransduction ◽  
Wear And Tear ◽  
Prevalent Disease ◽  
Local Shear ◽  
Mechanical Factors ◽  
Shear Strains

Osteoarthritis (OA) is a prevalent disease, afflicting 27 million people in the United States alone [1]. OA is commonly thought of as “wear and tear” of the joints caused by repeated compression and shear strains. The mechanical contribution to the onset and progression of OA is unknown; however, it is likely a result of an imbalance of cartilage homeostasis, represented by a shift in biochemical and mechanical factors that typically maintain healthy joints [2]. Cartilage homeostasis results in part from cellular mechanotransduction events, i.e. the conversion of mechanical stimuli into a biochemical response.

scholarly journals Simulations of Myenteric Neuron Dynamics in Response to Mechanical Stretch

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Donghua Liao ◽  
Jingbo Zhao ◽  
Hans Gregersen
Keyword(s):  
Large Scale ◽  
Visceral Pain ◽  
Mechanical Stretch ◽  
Compartment Model ◽  
Building Blocks ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Myenteric Neuron ◽  
Mechanoelectrical Transduction ◽  
Physiological Outcomes

Background. Intestinal sensitivity to mechanical stimuli has been studied intensively in visceral pain studies. The ability to sense different stimuli in the gut and translate these to physiological outcomes relies on the mechanosensory and transductive capacity of intrinsic intestinal nerves. However, the nature of the mechanosensitive channels and principal mechanical stimulus for mechanosensitive receptors are unknown. To be able to characterize intestinal mechanoelectrical transduction, that is, the molecular basis of mechanosensation, comprehensive mathematical models to predict responses of the sensory neurons to controlled mechanical stimuli are needed. This study aims to develop a biophysically based mathematical model of the myenteric neuron with the parameters constrained by learning from existing experimental data. Findings. The conductance-based single-compartment model was selected. The parameters in the model were optimized by using a combination of hand tuning and automated estimation. Using the optimized parameters, the model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. Conclusions. The model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. The model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network.

scholarly journals Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nicole Scholz ◽  
Chonglin Guan ◽  
Matthias Nieberler ◽  
Alexander Grotemeyer ◽  
Isabella Maiellaro ◽  
...  
Keyword(s):  
Brain Function ◽  
Direct Evidence ◽  
G Protein Coupled Receptors ◽  
Mechanical Stimuli ◽  
Ionotropic Receptor ◽  
Immunological Responses ◽  
Molecular Sensor ◽  
G Protein Coupled ◽  
Camp Levels ◽  
Receptor Family

Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.

scholarly journals A comparison of shear- and compression-induced mechanotransduction in SW1353 chondrocytes

2021 ◽  
Author(s):  
Hope D Welhaven ◽  
Carley N McCutchen ◽  
Ronald K June
Keyword(s):  
Mechanical Stimuli ◽  
Amino Acid Production ◽  
Biological Phenomenon ◽  
Beta Oxidation ◽  
Biochemical Responses ◽  
Cartilage Homeostasis ◽  
Cyclical Loading ◽  
Central Energy ◽  
Cartilage Breakdown

Mechanotransduction is a biological phenomenon where mechanical stimuli are converted to biochemical responses. A model system for studying mechanotransduction are the chondrocytes of articular cartilage. Breakdown of this tissue results in decreased mobility, increased pain, and reduced quality of life. Either disuse or overloading can disrupt cartilage homeostasis, but physiological cyclical loading promotes cartilage homeostasis. To model this, we exposed SW1353 cells to cyclical mechanical stimuli, shear and compression, for different durations of time (15 and 30 min). By utilizing liquid chromatography-mass spectroscopy (LC-MS), metabolomic profiles were generated detailing metabolite features and biological pathways that are altered in response to mechanical stimulation. In total, 1,457 metabolite features were detected. Statistical analyses identified several pathways of interest. Taken together, differences between experimental groups were associated with inflammatory pathways, lipid metabolism, beta-oxidation, central energy metabolism, and amino acid production. These findings expand our understanding of chondrocyte mechanotransduction under varying loading conditions and time periods.

scholarly journals A machine-vision approach for automated pain measurement at millisecond timescales

2020 ◽  
Author(s):  
Jessica Jones ◽  
William Foster ◽  
Colin Twomey ◽  
Justin Burdge ◽  
Osama Ahmed ◽  
...  
Keyword(s):  
High Speed ◽  
Neural Circuit ◽  
Inbred Mouse ◽  
Automatic Measurement ◽  
Dimensional Subspace ◽  
Mouse Strains ◽  
Mechanical Stimuli ◽  
Learning Approaches ◽  
Linear Discriminant ◽  
Noxious Stimuli

Objective and automatic measurement of pain in mice remains a barrier for discovery in both basic and translational neuroscience. Here we capture rapid paw kinematics during pain behavior in mice with high-speed videography and automated paw tracking with machine and deep learning approaches. Our statistical software platform, PAWS (Pain Assessment at Withdrawal Speeds), uses a univariate projection of paw position over time to automatically quantify fast paw dynamics at the onset of paw withdrawal and also lingering pain-related behaviors such as paw guarding and shaking. Applied to innocuous and noxious stimuli across six inbred mouse strains, a linear discriminant analysis reveals a two-dimensional subspace that separates painful from non-painful stimuli on one axis, and further distinguishes the severity of pain on the second axis. Automated paw tracking combined with PAWS reveals behaviorally-divergent mouse strains that display hypo- and hyper-sensitivity to mechanical stimuli. To demonstrate the efficacy of PAWS for detecting hypersensitivity to noxious stimuli, we chemogenetically activated pain-aversion neurons in the amygdala, which further separated the behavioral representation of pain-related behaviors along a low-dimensional path. Taken together, this automated pain quantification approach should increase the ease and objectivity of collecting rigorous behavioral data, and it is compatible with other neural circuit dissection tools for determining the mouse pain state.

scholarly journals Unusual characteristics of the receptor for the N sex factor-specific filamentous phage IKe

1975 ◽  
Vol 25 (3) ◽  
pp. 275-284 ◽  
Author(s):  
Sheena Dennison ◽  
S. Baumberg
Keyword(s):  
High Speed ◽  
Liquid Culture ◽  
Direct Evidence ◽  
Filamentous Phage ◽  
Limited Extent ◽  
N Transfer ◽  
Incompatibility Group ◽  
Transfer Frequency ◽  
Low Ionic Strength ◽  
Strength Medium

SUMMARYPlasmid-mediated sensitivity to filamentous phage IKe is shown to be a property exclusive to plasmids of the N incompatibility group. As with other sex factor-specific phages, IKe sensitivity results from the provision of a plasmid-encoded receptor. However, direct evidence for IKe adsorption to a sex pilus-like structure is so far lacking.Mutations in an N plasmid were obtained which affected IKe infect-ability and N transfer frequency simultaneously, though to different extents. IKe receptors could be removed to a limited extent by high speed blending, but only under more extreme conditions (higher speed and in low ionic strength medium) than F pili. As with F-specific filamentous phages, IKe adsorption was partially blocked by Zn2+.We tentatively suggest that the results accord with the IKe receptor being a sex pilus rather different from F and I pili (possibly in being much shorter in liquid culture), but other interpretations of these data are possible.

High Speed Shape Memory Alloy Activation

2012 ◽  
Author(s):  
Alexander Czechowicz ◽  
Jonas Böttcher ◽  
Sebastian Mojrzisch ◽  
Sven Langbein
Keyword(s):  
Shape Memory ◽  
Smart Materials ◽  
High Speed ◽  
Industrial Applications ◽  
Feedback Signal ◽  
Sma Actuators ◽  
Wide Range ◽  
Current Activation ◽  
Actual Shape ◽  
Control Feedback

Due to their ability to change into a previously imprinted actual shape through the means of thermal and electrical activation, shape memory alloys (SMA) are suitable as actuators. To apply these smart materials to a wide range of high-speed applications like valves or safety systems, an analysis of the application potential is required. The detection of inner electrical resistance of SMA actuators allows gauging the actuator’s stroke. By usage of a microcontroller a smart system without any hardware sensors can be realized which protects the system from overheating during high-current activation. The publication concentrates on different experimental data on high-speed actuation under 20ms and the potentials in the field of industrial applications. The paper gives an overview about different controlling methods for SMA-actuators, experiments concerning the resistance behavior of SMA and the development of systems using a resistance control feedback signal during high-speed activation.

Sign in / Sign up

Export Citation Format

Share Document