Research on comfortable driving posture of car drivers based on muscle biomechanics

This paper aims to solve the problem of optimal design on a comfortable human-machine arrangement of car drivers with different physical signs under dynamic manipulation. Based on the biomechanical characteristic of human skeletal muscle and Hill muscle mechanics model, this paper constructs the human seat musculoskeletal model of 5th, 50th, and 95th percentile physical signs of Chinese car drivers under dynamic manipulation. The six-degree-of-freedom flexible test bench was set up and the center composite method was used to optimize the number of experiments. The consistency and relevance analysis of the actual measurement and dynamic manipulation simulation was carried out to comprehensively analyze the human-machine arrangement parameters such as vehicle seat, pedal, and steering wheel, so as to realize the optimization design of the hard point size of comfortable driving posture and verify the rationality and applicability of the test results through the vehicle road test.

The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles

Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.

Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics

The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthrogryposis (DA), and TNNT1 and TNNT3 in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca2+ sensitivity of force or by inducing atrophy. Several potential therapeutic strategies are available to counter the effects of variants, such as troponin activators, introduction of wild-type protein through AAV gene therapy, and myosin modulation to improve muscle contraction. The mechanisms underlying the pathophysiological effects of the variants in skeletal troponin encoding genes are incompletely understood. Furthermore, limited knowledge is available on the structure of skeletal troponin. This review focusses on the physiology of slow and fast skeletal troponin and the pathophysiology of reported variants in skeletal troponin encoding genes. A better understanding of the pathophysiological effects of these variants, together with enhanced knowledge regarding the structure of slow and fast skeletal troponin, will direct the development of treatment strategies.

Optimized Torque Assistance During Walking With an Idealized Hip Exoskeleton

The hip muscles account for a great percentage of the total human energy expenditure during walking and many wearable devices have been developed in assisting the hip joint to reduce the metabolic Cost Of Transport (COT) for walking. However, the effectiveness of assisting the hip in only one direction (either flexion or extension) or both directions has not been systematically studied and the underlying muscle mechanics and energetics affected by the assistance are not well understood. In this study, human-exoskeleton simulation based optimizations were performed to find optimized hip assistance torque profiles for (1) unidirectional flexion assistance, (2) unidirectional extension assistance, and (3) bidirectional flexion and extension assistance. Our results show that the bidirectional assistance is the most effective in reducing the COT of walking (22.7% reduction) followed by flexion (19.2%) and extension (11.7%). The flexion assistance resulted in more COT saving than the output of its net work by 35.9%, which indicates that the negative work done (42.2% of its positive counterpart) also played an important role in reducing the COT. The bidirectional assistance also reduced the activations of the hip extensors to a great extent and shifted the activation pattern of the hip flexor (ilipsoas). These results can provide valuable information for optimal hip actuation (timing and profiles) and help exoskeleton designers make informed decisions.

The Super-Relaxed State and Length Dependent Activation in Porcine Myocardium

Rationale: Myofilament length dependent activation (LDA) is the key underlying mechanism of cardiac heterometric autoregulation, commonly referred as the Frank-Starling law of the heart. Although alterations in LDA are common in cardiomyopathic states, the precise structural and biochemical mechanisms underlying LDA remain unknown. Objective: Here, we examine the role of structural changes in the thick filament during diastole, in particular changes in the availability of myosin heads, in determining both calcium sensitivity and maximum contractile force during systole in permeabilized porcine cardiac fibers. Methods and Results: Permeabilized porcine fibers from ventricular myocardium were studied under relaxing conditions at short and long sarcomere length (SL) using muscle mechanics, biochemical measurements, and X-ray diffraction. Upon stretch, porcine myocardium showed the increased calcium sensitivity and maximum calcium activated force characteristic of LDA. Stretch increased diastolic ATP turnover, recruiting reserve myosin heads from the super-relaxed state (SRX) at longer SL. Structurally, X-ray diffraction studies in the relaxed-muscle confirmed a departure from the helical ordering of the thick-filament upon stretch which occurred concomitantly with a displacement of myosin heads towards actin, facilitating cross-bridge formation upon systolic activation. Mavacamten, a selective myosin-motor inhibitor known to weaken the transition to actin-bound power-generating states and to enrich the ordered SRX myosin population, reversed the structural effects of stretch on the thick-filament, blunting the mechanical consequences of stretch; mavacamten did not, however, prevent other structural changes associated with LDA in the sarcomere, such as decreased lattice spacing or troponin-displacement. Conclusions: Our findings strongly indicate that in ventricular muscle, LDA and its systolic consequences are dependent on the population of myosin heads competent to form cross-bridges and involves the recruitment of myosin heads from the reserve SRX pool during diastole.

Wearables-Only Analysis of Muscle and Joint Mechanics: An EMG-Driven Approach

Complex sensor arrays prohibit practical deployment of existing wearables-based algorithms for free-living analysis of muscle and joint mechanics. Machine learning techniques have been proposed as a potential solution, however, they are less interpretable and generalizable when compared to physics-based techniques. Herein, we propose a hybrid method utilizing inertial sensor- and electromyography (EMG)-driven simulation of muscle contraction to characterize knee joint and muscle mechanics during walking gait. Machine learning is used only to map a subset of measured muscle excitations to a full set thereby reducing the number of required sensors. We demonstrate the utility of the approach for estimating net knee flexion moment (KFM) as well as individual muscle moment and work during the stance phase of gait across nine unimpaired subjects. Across all subjects, KFM was estimated with 0.91 %BW·H RMSE and strong correlations (r = 0.87) compared to ground truth inverse dynamics analysis. Estimates of individual muscle moments were strongly correlated (r = 0.81-0.99) with a reference EMG-driven technique using optical motion capture and a full set of electrodes as were estimates of muscle work (r = 0.88-0.99). Implementation of the proposed technique in the current work included instrumenting only three muscles with surface electrodes (lateral and medial gastrocnemius and vastus medialis) and both the thigh and shank segments with inertial sensors. These sensor locations permit instrumentation of a knee brace/sleeve facilitating a practically deployable mechanism for monitoring muscle and joint mechanics with performance comparable to the current state-of-the-art.

Myosin dilated cardiomyopathy mutation S532P disrupts actomyosin interactions, leading to altered muscle kinetics, reduced locomotion, and cardiac dilation in Drosophila

Dilated cardiomyopathy (DCM), a life-threatening disease characterized by pathological heart enlargement, can be caused by myosin mutations that reduce contractile function. To better define the mechanistic basis of this disease, we employed the powerful genetic and integrative approaches available in Drosophila melanogaster. To this end, we generated and analyzed the first fly model of human myosin-induced DCM. The model reproduces the S532P human β-cardiac myosin heavy chain DCM mutation, which is located within an actin binding region of the motor domain. In concordance with the mutation's location at the actomyosin interface, steady-state ATPase and muscle mechanics experiments revealed that the S532P mutation reduces the rates of actin-dependent ATPase activity and actin binding and increases the rate of actin detachment. The depressed function of this myosin form reduces the number of cross-bridges during active wing beating, the power output of indirect flight muscles, and flight ability. Further, S532P mutant hearts exhibit cardiac dilation that is mutant gene dose-dependent. Our study shows that Drosophila can faithfully model various aspects of human DCM phenotypes and suggests that impaired actomyosin interactions in S532P myosin induce contractile deficits that trigger the disease.

Desmin intermediate filaments and tubulin detyrosination stabilize growing microtubules in the cardiomyocyte

The microtubule network of the cardiomyocyte exhibits specialized architecture, stability and mechanical behavior that accommodate the demands of working muscle cells. Stable, post-translationally detyrosinated microtubules are physical coupled to the sarcomere, the contractile apparatus of muscle, and resist sarcomere motion to regulate muscle mechanics and mechanosignaling. Control of microtubule growth and shrinkage dynamics represents a potential intermediate in the formation of a stable, physically coupled microtubule network, yet the molecular determinants that govern dynamics are unknown. Here we test the hypothesis that desmin intermediate filaments may stabilize growing microtubules at the sarcomere Z-disk in a detyrosination-dependent manner. Using a combination of biochemical assays and direct observation of microtubule plus-end dynamics in primary adult cardiomyocytes, we determine that: 1) tyrosination increases the frequency of microtubule depolymerization and reduces the pausing of microtubules at the Z-disk, leading to a more dynamic microtubule; and 2) desmin intermediate filaments stabilize both growing and shrinking microtubules specifically at the Z-disk and protect them from depolymerization. This stabilizes iteratively growing, detyrosinated microtubules between adjacent sarcomeres, which promotes the formation of high-energy microtubules that buckle between sarcomeres and elevates myocyte viscoelasticity. Our findings inform on how the tubulin code and intermediate filaments regulate microtubule dynamics, and provide mechanism to the establishment of a spatially organized, physically coupled, and long-lived microtubule network in the cardiomyocyte.