Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles

This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ~50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses. The stimulation resulted in a decrease in the titin-based passive force. The amounts of fragmented titin were unchanged by the stimulation. Protein kinase Cα-treatment increased the passive force in stimulated fibers to resting levels. The stimulation had no effect on the maximum Ca2+-activated force (max Ca2+ force) at a sarcomere length (SL) of 2.4 μm and decreased myofibrillar (my)-Ca2+ sensitivity at 2.6-μm SL. Stretching the SL to 3.0 μm led to the augmentation of the max Ca2+ force and my-Ca2+ sensitivity in both rested and stimulated fibers. For the max Ca2+ force, the extent of the increase was smaller in stimulated than in rested fibers, whereas for my-Ca2+ sensitivity, it was higher in stimulated than in rested fibers. These results suggest that vigorous isometric contractions decrease the titin-based passive force, possibly because of a reduction in phosphorylation by protein kinase Cα, and that the decreased titin stiffness may contribute, at least in part, to muscle fatigue.

Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart

Sarcomeric contraction in cardiomyocytes serves as the basis for the heart’s pump functions. It has generally been considered that in cardiac muscle as well as in skeletal muscle, sarcomeres equally contribute to myofibrillar dynamics in myocytes at varying loads by producing similar levels of active and passive force. In the present study, we expressed α-actinin–AcGFP in Z-disks to analyze dynamic behaviors of sequentially connected individual sarcomeres along a myofibril in a left ventricular (LV) myocyte of the in vivo beating mouse heart. To quantify the magnitude of the contribution of individual sarcomeres to myofibrillar dynamics, we introduced the novel parameter “contribution index” (CI) to measure the synchrony in movements between a sarcomere and a myofibril (from −1 [complete asynchrony] to 1 [complete synchrony]). First, CI varied markedly between sarcomeres, with an average value of ∼0.3 during normal systole. Second, when the movements between adjacent sarcomeres were asynchronous (CI < 0), a sarcomere and the ones next to the adjacent sarcomeres and farther away moved in synchrony (CI > 0) along a myofibril. Third, when difference in LV pressure in diastole and systole (ΔLVP) was lowered to <10 mm Hg, diastolic sarcomere length increased. Under depressed conditions, the movements between adjacent sarcomeres were in marked asynchrony (CI, −0.3 to −0.4), and, as a result, average CI was linearly decreased in association with a decrease in ΔLVP. These findings suggest that in the left ventricle of the in vivo beating mouse heart, (1) sarcomeres heterogeneously contribute to myofibrillar dynamics due to an imbalance of active and passive force between neighboring sarcomeres, (2) the force imbalance is pronounced under depressed conditions coupled with a marked increase in passive force and the ensuing tug-of-war between sarcomeres, and (3) sarcomere synchrony via the distal intersarcomere interaction regulates the heart's pump function in coordination with myofibrillar contractility.

Titin N2A Domain and Its Interactions at the Sarcomere

Titin is a giant protein in the sarcomere that plays an essential role in muscle contraction with actin and myosin filaments. However, its utility goes beyond mechanical functions, extending to versatile and complex roles in sarcomere organization and maintenance, passive force, mechanosensing, and signaling. Titin’s multiple functions are in part attributed to its large size and modular structures that interact with a myriad of protein partners. Among titin’s domains, the N2A element is one of titin’s unique segments that contributes to titin’s functions in compliance, contraction, structural stability, and signaling via protein–protein interactions with actin filament, chaperones, stress-sensing proteins, and proteases. Considering the significance of N2A, this review highlights structural conformations of N2A, its predisposition for protein–protein interactions, and its multiple interacting protein partners that allow the modulation of titin’s biological effects. Lastly, the nature of N2A for interactions with chaperones and proteases is included, presenting it as an important node that impacts titin’s structural and functional integrity.

Muscle ankyrin repeat protein 1 (MARP1) locks titin to the sarcomeric thin filament and is a passive force regulator

Muscle ankyrin repeat protein 1 (MARP1) is frequently up-regulated in stressed muscle, but its effect on skeletal muscle function is poorly understood. Here, we focused on its interaction with the titin–N2A element, found in titin’s molecular spring region. We show that MARP1 binds to F-actin, and that this interaction is stronger when MARP1 forms a complex with titin–N2A. Mechanics and super-resolution microscopy revealed that MARP1 “locks” titin–N2A to the sarcomeric thin filament, causing increased extension of titin’s elastic PEVK element and, importantly, increased passive force. In support of this mechanism, removal of thin filaments abolished the effect of MARP1 on passive force. The clinical relevance of this mechanism was established in diaphragm myofibers of mechanically ventilated rats and of critically ill patients. Thus, MARP1 regulates passive force by locking titin to the thin filament. We propose that in stressed muscle, this mechanism protects the sarcomere from mechanical damage.

To drain or not to drain: the association between residual intraperitoneal gas and post-laparoscopic shoulder pain for laparoscopic cholecystectomy

Residual intra-peritoneal gas may be associated with post-laparoscopic shoulder pain (PLSP), which is a frequently and disturbance compliant after surgery. Herein, we aimed to examine whether expiring residual gas via a surgical drain reduces the frequency and intensity of PLSP in the first day after laparoscopic cholecystectomy. 448 participants were enrolled in this prospective cohort study. The incidence and severity of PLSP after surgery were recorded. Of these, the cumulative incidence of PLSP in the drain group was lower particularly at the 12th postoperative hour (18.3% vs. 27.6%; P = 0.022), 24th postoperative hour (28.8% vs. 38.1%; P = 0.039), and throughout the first postoperative day (P = 0.035). The drain group had less severe PLSP (crude Odds ratio, 0.66; P = .036). After adjustment using inverse probability of treatment weighting, the drain group also had a significant lower PLSP incidence (adjusted hazard ratio = 0.61, P < 0.001), and less severe PLSP (adjusted odds ratio = 0.56, P < 0.001). In conclusion, the maneuver about passive force to expel residual gas, surgical drain use, contributes to reduce the incidence and severity of PLSP, suggesting that to minimize residual gas at the end of surgery is useful to attenuate PLSP.

Five-Fingered Passive Force Feedback Glove Using a Variable Ratio Lever Mechanism

Force feedback gloves allow users to touch and manipulate virtual objects intuitively. Compared with gloves providing active feedback force, gloves with passive feedback force are promising in terms of safety and low weight, but simulating the variable stiffness of virtual objects is more challenging. Addressing this difficulty, we propose a five-fingered glove with passive force feedback employing a variable ratio lever mechanism. The stiffness of the proposed glove is tuned by changing the structural stiffness of this mechanism rather than by applying torque control at each joint of the finger. The switch between free and constrained space is realized in real time by locking/unlocking the revolute joints of the glove using a servo motor. Furthermore, a predictive control mode is proposed to reduce the response time of the control system, and the actual response time is less than the limit of the delay (45 ms) that humans can perceive between visual and haptic stimuli. Experimental results show that the linear stiffness at the fingertip ranges from 0.89 to 619.89 N/m, and the maximum backdrive force of the proposed glove is less than 0.147 N.

Age-related reductions in the number of serial sarcomeres contribute to shorter fascicle lengths but not elevated passive tension

We investigated age-related changes to fascicle length (FL), sarcomere length (SL), and serial sarcomere number (SSN), and how this affects passive force. Following mechanical testing to determine passive force, the medial gastrocnemius muscle of young (n=9) and old (n=8) Fisher 344BN hybrid rats was chemically fixed at the optimal muscle length for force production; individual fascicles were dissected for length measurement, and laser diffraction was used to assess SL. Old rats had ∼14% shorter FL than young, which was driven by a ∼10% reduction in SSN, with no difference in SL (∼4%). Passive force was greater in the old compared to young rats at long muscle lengths. Shorter FL and reduced SSN in the old rats could not entirely explain increased passive forces for absolute length changes, owing to a slight reduction in SL in old, resulting in similar SL at long muscle lengths.

Modeling and Development of Passively Adaptive Assistive Tools for the Assembly of Press-Fit Components

This article discusses passive mechanical architectures for accuracy correction during assembly operations. A specific solution for passive force generation with thresholds is presented. Then, the kinematics of several rotational and translational mechanisms is presented. Afterwards, a case study is introduced and the design of a prototype is presented together with some tests performed on a spark plug assembly task.