Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C

The influences of [Ca(2+)] and Ca(2+) dissociation rate from troponin C (TnC) on the kinetics of contraction (k(Ca)) activated by photolysis of a caged Ca(2+) compound in skinned fast-twitch psoas and slow-twitch soleus fibers from rabbits were investigated at 15 degrees C. Increasing the amount of Ca(2+) released increased the amount of force in psoas and soleus fibers and increased k(Ca) in a curvilinear manner in psoas fibers approximately 5-fold but did not alter k(Ca) in soleus fibers. Reconstituting psoas fibers with mutants of TnC that in solution exhibited increased Ca(2+) affinity and approximately 2- to 5-fold decreased Ca(2+) dissociation rate (M82Q TnC) or decreased Ca(2+) affinity and approximately 2-fold increased Ca(2+) dissociation rate (NHdel TnC) did not affect maximal k(Ca). Thus the influence of [Ca(2+)] on k(Ca) is fiber type dependent and the maximum k(Ca) in psoas fibers is dominated by kinetics of cross-bridge cycling over kinetics of Ca(2+) exchange with TnC.     

On the relative importance of specific and non-specific approaches to oral microbial adhesion

Abstract In this paper, it is suggested that specificity and non-specificity in (oral) microbial adhesion are different expressions for the same phenomena. It is argued that the same basic, physico-chemical forces are responsible for so-called 'non-specific' and 'specific' binding and that from a physico-chemical point of view the distinction between the two is an artificial one. Non-specific interactions arise from Van der Waals and electrostatic forces and hydrogen bonding, and originate from the entire cell. A specific bond consists of a combination of the same type of Van der Waals and electrostatic forces and hydrogen bonding, now originating from highly localized chemical groups, which together form a stereo-chemical combination. The absence or presence of specific receptor sites on microbial cell surfaces must therefore be reflected in the overall, non-specific surface properties of cells as well. This point is illustrated by showing that glucanbinding lectins on mutans streptococcal strains may determine the pH dependence of the zeta potentials of these cells. When studying microbial adhesion, a non-specific approach may be better suited to explain adhesion to inert substrata, whereas a specific approach may be preferred in case of adhesion to adsorbed protein films. Adhesion is, however, not as important in plaque formation in the human oral cavity as is retention, because low shear force periods. during which adhesion presumably occurs, are followed by high shear force periods, during which adhering cells must withstand these detachment forces. Evidence is provided that such detachment will be through cohesive failure in the pellicle mass, the properties of which are conditioned by the overall, non-specific substratum properties. Therefore, in vivo plaque formation may be more readily explained by a non-specific approach.     

Effect of load position on muscle forces,internal loads and stability of the human spine in upright postures

A novel kinematics-based approach coupled with a non-linear finite element model was used to investigate the effect of changes in the load position and posture on muscle activity, internal loads and stability margin of the human spine in upright standing postures. In addition to 397 N gravity, external loads of 195 and 380 N were considered at different lever arms and heights. Muscle forces, internal loads and stability margin substantially increased as loads displaced anteriorly away from the body. Under same load magnitude and location, adopting a kyphotic posture as compared with a lordotic one increased muscle forces, internal loads and stability margin. An increase in the height of a load held at a fixed lever arm substantially diminished system stability thus requiring additional muscle activations to maintain the same margin of stability. Results suggest the importance of the load position and lumbar posture in spinal biomechanics during various manual material handling operations.     

Atomic contacts in protein structures. A detailed analysis of atomic radii, packing, and overlaps

A rigorous quantitative assessment of atomic contacts and packing in native protein structures is presented. The analysis is based on optimized atomic radii derived from a set of high-resolution protein structures and reveals that the distribution of atomic contacts and overlaps is a structural constraint in proteins, irrespective of structural or functional classification and size. Furthermore, a newly developed method for calculating packing properties is introduced and applied to sets of protein structures at different levels of resolution. The results show that limited resolution yields decreasing packing quality, which underscores the relevance of packing considerations for structure prediction, design, dynamics, and docking.     

A coupled framework of in situ and in silico analysis reveals the role of lateral force transmission in force production in volumetric muscle loss injuries

Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in wound location. Regenerative medicine offers promising alternative treatments, but there is little understanding of the correlation between magnitude of VML injuries and corresponding functional deficits that must be addressed. There is a need for a tool that can elucidate the relationship between VML injury and force loss, as well as the impact on specific mechanisms responsible for force production. The purpose of this study was to develop a novel coupled framework of in situ and in silico methods to more precisely understand the relationship between injury location and force production deficits. We created a three-dimensional finite-element model of the pennate latissimus dorsi (LD) muscle in the rat and validated the model experimentally. We found that the model’s prediction (2.6 N/g Model I, 2.1 N/g Model V) compared favorably to in situ testing of isometric force generation of the injured rat LD muscle (2.8 ± 0.3 N/g Experimental I, 2.0 ± 0.2 N/g Experimental V). Further model analysis revealed that the contribution from lateral and longitudinal force transmission to the total force varied with injury location and led to a greater understanding of the mechanisms responsible for VML-related force deficits. In the future, the coupled computational and experimental framework can be used to inform development of preclinical VML injury models that better recapitulate the spectrum of VML injuries observed in affected patients, and the mechanistic insight can accelerate the creation of improved regenerative therapeutics for VML injuries.     

A biomechanical model for analysis of muscle force,power output and lower jaw motion in fishes

Fish skulls are complex kinetic systems with movable components that are powered by muscles. Cranial muscles for jaw closing pull the mandible around a point of rotation at the jaw joint using a third-order lever mechanism. The present study develops a lever model for the jaw of fishes that uses muscle design and the Hill equation for nonlinear length-tension properties of muscle to calculate dynamic power output. The model uses morphometric data on skeletal dimensions and muscle proportions in order to predict behavior and force transmission mediated by lever action. The computer model calculates a range of dynamic parameters of jaw function including muscle force, torque, effective mechanical advantage, jaw velocity, bite duration, bite force, work and power. A complete list of required morphometrics is presented and a software program (MandibLever 2.0) is available for implementing lever analysis. Results show that simulations yield kinematics and timing profiles similar to actual fish feeding events. Simulation of muscle properties shows that mandibles reach their peak velocity near the start of jaw closing, peak force at the end of jaw closing, and peak power output at about 25% of the closing cycle time. Adductor jaw muscles with different mechanical designs must have different contractile properties and/or different muscle activity patterns to coordinate jaw closing. The effective mechanical advantage calculated by the model is considerably lower than the mechanical advantage estimated from morphological lever ratios, suggesting that previous studies of morphological lever ratios have overestimated force and underestimated velocity transmission to the mandible. A biomechanical model of jaw closing can be used to interpret the mechanics of a wide range of jaw mechanisms and will enable studies of the functional results of developmental and evolutionary changes in skull morphology and physiology.