Mechanical gating of the auditory transduction channel TMC1 involves the fourth and sixth transmembrane helices

The transmembrane channel-like (TMC) 1 and 2 proteins play a central role in auditory transduction, forming ion channels that convert sound into electrical signals. However, the molecular mechanism of their gating remains unknown. Here, using predicted structural models as a guide, we probed the effects of twelve mutations on the mechanical gating of the transduction currents in native hair cells of Tmc1/2-null mice expressing virally introduced TMC1 variants. Whole-cell electrophysiological recordings revealed that mutations within the pore-lining transmembrane (TM) helices 4 and 6 modified gating, reducing the force sensitivity or shifting the open probability of the channels, or both. For some of the mutants, these changes were accompanied by a change in single-channel conductance. Our observations are in line with a model wherein conformational changes in the TM4 and TM6 helices are involved in the mechanical gating of the transduction channel.

Research on the Force-Sensitive Characteristic of InAs QD Embedded in HEMT

A force-sensitive structure of an InAs Quantum Dot (QD) embedded in a high electron mobility transistor (HEMT) is presented in this paper. The size of an InAs QD is about 30 nm prepared by the S-K growth mode, and the force-sensitive structure is fabricated by molecular beam epitaxy (MBE). The force-sensitivity characteristic of the QD HEMT is studied by the electrical and mechanical properties. The electrical characteristics show that the InAs QD-HEMT has linear, cut-off, and saturation operating states, and produces different output currents under different gate voltages, which shows that the structure is reasonable. Furthermore, the results of the output characteristics under different pressure show that the output voltage of the QD-HEMT decreases with the increase in pressure, which indicates that the InAs QD-HEMT has a vital mechanical–electrical coupling characteristic. The output voltage of the InAs QD-HEMT in the range of 0–100 kPa shows that the sensitivity was 1.09 mV/kPa.

Design and Implementation of Symmetric Legged Robot for Highly Dynamic Jumping and Impact Mitigation

Aiming at highly dynamic locomotion and impact mitigation, this paper proposes the design and implementation of a symmetric legged robot. Based on the analysis of the three-leg topology in terms of force sensitivity, force production, and impact mitigation, the symmetric leg was designed and equipped with a high torque density actuator, which was assembled by a custom motor and two-stage planetary. Under the kinematic and dynamic constraints of the robot system, a nonlinear optimization for high jumping and impact mitigation is proposed with consideration of the peak impact force at landing. Finally, experiments revealed that the robot achieved a jump height of 1.8 m with a robust landing, and the height was equal to approximately three times the leg length.

Hypertrophic cardiomyopathy mutations in the pliant and light chain-binding regions of the lever arm of human β-cardiac myosin have divergent effects on myosin function

ABSTRACTMutations in the lever arm of β-cardiac myosin are a frequent cause of hypertrophic cardiomyopathy (HCM), a disease characterized by hypercontractility and eventual hypertrophy of the left ventricle. Here, we studied five such mutations: three in the pliant region of the lever arm (D778V, L781P, and S782N) and two in the light chain-binding region (A797T and F834L). We investigated their effects on both motor function and myosin S2 tail-based autoinhibition. The pliant region mutations had varying effects on the motor function of a myosin construct lacking the S2 tail: overall, D778V increased power output, L781P reduced power output, and S782N had little effect on power output, while all three reduced the external force sensitivity of the actin detachment rate. With a myosin containing the motor domain and the proximal S2 tail, the pliant region mutations also attenuated autoinhibition in the presence of filamentous actin but had no impact in the absence of actin. By contrast, the light chain-binding region mutations had little effect on motor activity but produced marked reductions in autoinhibition in both the presence and absence of actin. Thus, mutations in the lever arm of β-cardiac myosin have divergent allosteric effects on myosin function, depending on whether they are in the pliant or light chain-binding regions.

Tension vector and structure matrix associated force sensitivity of a 6-DOF cable-driven parallel robot

This paper investigates the force sensitivity of 6-DOF cable-driven parallel robots (CDPRs) in order to propose a better force measurement device. Kinematics and dynamics for a CDPR of n-DOF are deduced and formulated, and algorithms for calculating the cable tension are developed. Then, by defining geometrical parameters related to the dimensions and configurations of the CDPRs, optimal methods for determining force sensitivity with respect to the structure matrix and twist vector of the 6-DOF CDPRs with two different moving platforms (i.e. a cubic-shaped, and a flat moving platform) are proposed. By using numerical examples integrated with external twists obtained from wind tunnel tests, simulations and analysis for the two type of 6-DOF CDPRs are carried out. The simulation results help identify the optimal dimensions that can be used to design 6-DOF-CDPR-based force measuring devices with high force sensitivity. Experiment validation is also conducted to verify the method proposed in this paper.

Force sensitivity analysis and scale design of Stewart parallel manipulator

There are many indices for evaluating the operational performance of parallel robots, but most of them start from kinematics and rarely pay special attention to the force transmission process. After studying the relationship and characteristics of the forward and reverse force transmission of the Stewart parallel manipulator under quasi-static conditions, three new indices are proposed in this paper, which are forward force sensitivity, reverse force sensitivity, and overall force sensitivity. Subsequently, the influences of six parameters on the overall force sensitivity index are analyzed. Furthermore, this paper propose three new structural optimization design schemes based on the three newly proposed indices. Finally, it is verified experimentally that the unit reverse force sensitivity of a single joint is consistent with the theory and the error between the theoretical and experimental values is obtained.

Towards a Fully Automated Scanning Probe Microscope for Biomedical Applications

The increase in capabilities of Scanning Probe Microscopy (SPM) has resulted in a parallel increase in complexity that limits the use of this technique outside of specialised research laboratories. SPM automation could substantially expand its application domain, improve reproducibility and increase throughput. Here, we present a bottom-up design in which the combination of positioning stages, orientation, and detection of the probe produces an SPM design compatible with full automation. The resulting probe microscope achieves sub-femtonewton force sensitivity whilst preserving low mechanical drift (2.0±0.2 nm/min in-plane and 1.0±0.1 nm/min vertically). The additional integration of total internal reflection microscopy, and the straightforward operations in liquid, make this instrument configuration particularly attractive to future biomedical applications.