ResearchPad - mechanical-energy https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[How global DNA unwinding causes non-uniform stress distribution and melting of DNA]]> https://www.researchpad.co/article/elastic_article_14712 DNA unwinding is an important process that controls binding of proteins, gene expression and melting of double-stranded DNA. In a series of all-atom MD simulations on two DNA molecules containing a transcription start TATA-box sequence we demonstrate that application of a global restraint on the DNA twisting dramatically changes the coupling between helical parameters and the distribution of deformation energy along the sequence. Whereas only short range nearest-neighbor coupling is observed in the relaxed case, long-range coupling is induced in the globally restrained case. With increased overall unwinding the elastic deformation energy is strongly non-uniformly distributed resulting ultimately in a local melting transition of only the TATA box segment during the simulations. The deformation energy tends to be stored more in cytidine/guanine rich regions associated with a change in conformational substate distribution. Upon TATA box melting the deformation energy is largely absorbed by the melting bubble with the rest of the sequences relaxing back to near B-form. The simulations allow us to characterize the structural changes and the propagation of the elastic energy but also to calculate the associated free energy change upon DNA unwinding up to DNA melting. Finally, we design an Ising model for predicting the local melting transition based on empirical parameters. The direct comparison with the atomistic MD simulations indicates a remarkably good agreement for the predicted necessary torsional stress to induce a melting transition, for the position and length of the melted region and for the calculated associated free energy change between both approaches.

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<![CDATA[Changes in Achilles tendon stiffness and energy cost following a prolonged run in trained distance runners]]> https://www.researchpad.co/article/5b87836b40307c3c4509766e

During prolonged running, the magnitude of Achilles tendon (AT) length change may increase, resulting in increased tendon strain energy return with each step. AT elongation might also affect the magnitude of triceps surae (TS) muscle shortening and shortening velocity, requiring greater activation and increased muscle energy cost. Therefore, we aimed to quantify the tendon strain energy return and muscle energy cost necessary to allow energy storage to occur prior to and following prolonged running. 14 trained male (n = 10) and female (n = 4) distance runners (24±4 years, 1.72±0.09 m, 61±10 kg, V˙O2max 64.6±5.8 ml•kg-1•min-1) ran 90 minutes (RUN) at approximately 85% of lactate threshold speed (sLT). Prior to and following RUN, AT stiffness and running energy cost (Erun) at 85% sLT were determined. AT energy return was calculated from AT stiffness, measured with dynamometry and ultrasound and estimated TS force during stance. TS energy cost was estimated on the basis of AT force and assumed crossbridge mechanics and energetics. Following RUN, AT stiffness was reduced from 328±172 N•mm-1 to 299±148 N•mm-1 (p = 0.022). Erun increased from 4.56±0.32 J•kg-1•m-1 to 4.62±0.32 J•kg-1•m-1 (p = 0.049). Estimated AT energy return was not different following RUN (p = 0.99). Estimated TS muscle energy cost increased significantly by 11.8±12.3 J•stride-1, (p = 0.0034), accounting for much of the post-RUN increase in Erun (8.6±14.5 J•stride-1,r2 = 0.31). These results demonstrate that a prolonged, submaximal run can reduce AT stiffness and increase Erun in trained runners, and that the elevated TS energy cost contributes substantially to the elevated Erun.

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<![CDATA[Elastic Free Energy Drives the Shape of Prevascular Solid Tumors]]> https://www.researchpad.co/article/5989db13ab0ee8fa60bcc98b

It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth.

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<![CDATA[The Role of Arch Compression and Metatarsophalangeal Joint Dynamics in Modulating Plantar Fascia Strain in Running]]> https://www.researchpad.co/article/5989da99ab0ee8fa60ba2d82

Elastic energy returned from passive-elastic structures of the lower limb is fundamental in lowering the mechanical demand on muscles during running. The purpose of this study was to investigate the two length-modulating mechanisms of the plantar fascia, namely medial longitudinal arch compression and metatarsophalangeal joint (MPJ) excursion, and to determine how these mechanisms modulate strain, and thus elastic energy storage/return of the plantar fascia during running. Eighteen runners (9 forefoot and 9 rearfoot strike) performed three treadmill running trials; unrestricted shod, shod with restricted arch compression (via an orthotic-style insert), and barefoot. Three-dimensional motion capture and ground reaction force data were used to calculate lower limb kinematics and kinetics including MPJ angles, moments, powers and work. Estimates of plantar fascia strain due to arch compression and MPJ excursion were derived using a geometric model of the arch and a subject-specific musculoskeletal model of the plantar fascia, respectively. The plantar fascia exhibited a typical elastic stretch-shortening cycle with the majority of strain generated via arch compression. This strategy was similar in fore- and rear-foot strike runners. Restricting arch compression, and hence the elastic-spring function of the arch, was not compensated for by an increase in MPJ-derived strain. In the second half of stance the plantar fascia was found to transfer energy between the MPJ (energy absorption) and the arch (energy production during recoil). This previously unreported energy transfer mechanism reduces the strain required by the plantar fascia in generating useful positive mechanical work at the arch during running.

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<![CDATA[Including Thermal Fluctuations in Actomyosin Stable States Increases the Predicted Force per Motor and Macroscopic Efficiency in Muscle Modelling]]> https://www.researchpad.co/article/5989dacaab0ee8fa60bb3ba0

Muscle contractions are generated by cyclical interactions of myosin heads with actin filaments to form the actomyosin complex. To simulate actomyosin complex stable states, mathematical models usually define an energy landscape with a corresponding number of wells. The jumps between these wells are defined through rate constants. Almost all previous models assign these wells an infinite sharpness by imposing a relatively simple expression for the detailed balance, i.e., the ratio of the rate constants depends exponentially on the sole myosin elastic energy. Physically, this assumption corresponds to neglecting thermal fluctuations in the actomyosin complex stable states. By comparing three mathematical models, we examine the extent to which this hypothesis affects muscle model predictions at the single cross-bridge, single fiber, and organ levels in a ceteris paribus analysis. We show that including fluctuations in stable states allows the lever arm of the myosin to easily and dynamically explore all possible minima in the energy landscape, generating several backward and forward jumps between states during the lifetime of the actomyosin complex, whereas the infinitely sharp minima case is characterized by fewer jumps between states. Moreover, the analysis predicts that thermal fluctuations enable a more efficient contraction mechanism, in which a higher force is sustained by fewer attached cross-bridges.

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<![CDATA[Effects of a leaf spring structured midsole on joint mechanics and lower limb muscle forces in running]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbf31

To enhance running performance in heel-toe running, a leaf spring structured midsole shoe (LEAF) has recently been introduced. The purpose of this study was to investigate the effect of a LEAF compared to a standard foam midsole shoe (FOAM) on joint mechanics and lower limb muscle forces in overground running. Nine male long-distance heel strike runners ran on an indoor track at 3.0 ± 0.2 m/s with LEAF and FOAM shoes. Running kinematics and kinetics were recorded during the stance phase. Absorbed and generated energy (negative and positive work) of the hip, knee and ankle joint as well as muscle forces of selected lower limb muscles were determined using a musculoskeletal model. A significant reduction in energy absorption at the hip joint as well as energy generation at the ankle joint was found for LEAF compared to FOAM. The mean lower limb muscle forces of the m. soleus, m. gastrocnemius lateralis and m. gastrocnemius medialis were significantly reduced for LEAF compared to FOAM. Furthermore, m. biceps femoris showed a trend of reduction in running with LEAF. The remaining lower limb muscles analyzed (m. gluteus maximus, m. rectus femoris, m. vastus medialis, m. vastus lateralis, m. tibialis anterior) did not reveal significant differences between the shoe conditions. The findings of this study indicate that LEAF positively influenced the energy balance in running by reducing lower limb muscle forces compared to FOAM. In this way, LEAF could contribute to an overall increased running performance in heel-toe running.

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<![CDATA[Characterizing the Mechanical Properties of Running-Specific Prostheses]]> https://www.researchpad.co/article/5989da5dab0ee8fa60b90572

The mechanical stiffness of running-specific prostheses likely affects the functional abilities of athletes with leg amputations. However, each prosthetic manufacturer recommends prostheses based on subjective stiffness categories rather than performance based metrics. The actual mechanical stiffness values of running-specific prostheses (i.e. kN/m) are unknown. Consequently, we sought to characterize and disseminate the stiffness values of running-specific prostheses so that researchers, clinicians, and athletes can objectively evaluate prosthetic function. We characterized the stiffness values of 55 running-specific prostheses across various models, stiffness categories, and heights using forces and angles representative of those measured from athletes with transtibial amputations during running. Characterizing prosthetic force-displacement profiles with a 2nd degree polynomial explained 4.4% more of the variance than a linear function (p<0.001). The prosthetic stiffness values of manufacturer recommended stiffness categories varied between prosthetic models (p<0.001). Also, prosthetic stiffness was 10% to 39% less at angles typical of running 3 m/s and 6 m/s (10°-25°) compared to neutral (0°) (p<0.001). Furthermore, prosthetic stiffness was inversely related to height in J-shaped (p<0.001), but not C-shaped, prostheses. Running-specific prostheses should be tested under the demands of the respective activity in order to derive relevant characterizations of stiffness and function. In all, our results indicate that when athletes with leg amputations alter prosthetic model, height, and/or sagittal plane alignment, their prosthetic stiffness profiles also change; therefore variations in comfort, performance, etc. may be indirectly due to altered stiffness.

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<![CDATA[Mechanical Energy Recovery during Walking in Patients with Parkinson Disease]]> https://www.researchpad.co/article/5989da83ab0ee8fa60b9b7e9

The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years) with bilateral symptoms (H&Y ≥II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62±3 years) walked both at their ‘preferred’ and ‘slow’ speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (Wp), total (WtotCM) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of WtotCM and Wp with knee ROM and in particular with knee extension in terminal stance phase. Wk and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both Wp and WtotCM. Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.

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<![CDATA[Mechanical Signals Inhibit Growth of a Grafted Tumor In Vivo: Proof of Concept]]> https://www.researchpad.co/article/5989da3eab0ee8fa60b88f79

In the past ten years, many studies have shown that malignant tissue has been “normalized” in vitro using mechanical signals. We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a “constraint field” on tumor growth. The human breast cancer cell line, MDA MB 231, admixed with ferric nanoparticles was grafted subcutaneously in Nude mice. The magnetizable particles rapidly surrounded the growing tumor. Two permanent magnets located on either side of the tumor created a gradient of magnetic field. Magnetic energy is transformed into mechanical energy by the particles acting as “bioactuators”, applying a constraint field and, by consequence, biomechanical stress to the tumor. This biomechanical treatment was applied 2 hours/day during 21 days, from Day 18 to Day 39 following tumor implantation. The study lasted 74 days. Palpable tumor was measured two times a week. There was a significant in vivo difference between the median volume of treated tumors and untreated controls in the mice measured up to D 74 (D 59 + population): (529 [346; 966] mm3 vs 1334 [256; 2106] mm3; p = 0.015), treated mice having smaller tumors. The difference was not statistically significant in the group of mice measured at least to D 59 (D 59 population). On ex vivo examination, the surface of the tumor mass, measured on histologic sections, was less in the treated group, G1, than in the control groups: G2 (nanoparticles, no magnetic field), G3 (magnetic field, no nanoparticles), G4 (no nanoparticles, no magnetic field) in the D 59 population (Median left surface was significantly lower in G1 (5.6 [3.0; 42.4] mm2, p = 0.005) than in G2 (20.8 [4.9; 34.3]), G3 (16.5 [13.2; 23.2]) and G4 (14.8 [1.8; 55.5]); Median right surface was significantly lower in G1 (4.7 [1.9; 29.2] mm2, p = 0.015) than in G2 (25.0 [5.2; 55.0]), G3 (18.0 [14.6; 35.2]) and G4 (12.5 [1.5; 51.8]). There was no statistically significant difference in the day 59+ population. This is the first demonstration of the effect of stress on tumor growth in vivo suggesting that biomechanical intervention may have a high translational potential as a therapy in locally advanced tumors like pancreatic cancer or primary hepatic carcinoma for which no effective therapy is currently available.

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<![CDATA[Anaerobic metabolism during short all-out efforts in tethered running: Comparison of energy expenditure and mechanical parameters between different sprint durations for testing]]> https://www.researchpad.co/article/5989db5dab0ee8fa60be04eb

This study’s aims to verify the energy expenditure, metabolic distress and usefulness to evaluate the anaerobic constructs for different all-out durations in running efforts. Twelve active male underwent four testing sessions, one for familiarization and three performing one all-out (AO) tethered running sprint lasting 30s, 20s or 10s. Oxygen consumption, excess post exercise oxygen consumption, and lactate production were retained to analyse metabolic function, together with mechanical power and work as performance parameters. Paired results were compared via one-way ANOVA for repeated measures (Tukey-HSD post-hoc), effect sizes and ICC for absolute agreement. Statistical significance was accepted at p ≤ 0.05. Despite total and energy expenditure from oxidative pathway being significantly higher for longer durations (p < 0.001; ES > 0.7), glycolytic energy expenditure presented an agreement between AO30s and AO20s (ICC-A = 0.63*), while the paired comparisons to AO10s have presented significant differences (p < 0.01; ES > 1.0). Phosphagen energy expenditure were similar between all-out durations (p = 0.12; ICC-A = 0.62*; ES < 0.5). Maximum mechanical power was higher in AO10s than in AO30s (p = 0.03; ES = 0.6), not being different between AO10s and AO20s (p = 0.67; ICC-A = 0.88*; ES = 0.2) and between AO20s and AO30s (p = 0.18; ICC-A = 0.56*; ES = 0.4). In addition, agreement between work in the first ten seconds was confirmed via ICC only between AO10s and AO20s (p = 0.50; ICC-A = 0.86*; ES = 0.3), but not for the other paired comparisons (p < 0.1; ICC < 0.45; ES > 0.5). AO20s is a better alternative to estimate anaerobic power and capacity in one single test, with similar oxidative demand than AO30s.

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<![CDATA[Sensory Agreement Guides Kinetic Energy Optimization of Arm Movements during Object Manipulation]]> https://www.researchpad.co/article/5989db33ab0ee8fa60bd2415

The laws of physics establish the energetic efficiency of our movements. In some cases, like locomotion, the mechanics of the body dominate in determining the energetically optimal course of action. In other tasks, such as manipulation, energetic costs depend critically upon the variable properties of objects in the environment. Can the brain identify and follow energy-optimal motions when these motions require moving along unfamiliar trajectories? What feedback information is required for such optimal behavior to occur? To answer these questions, we asked participants to move their dominant hand between different positions while holding a virtual mechanical system with complex dynamics (a planar double pendulum). In this task, trajectories of minimum kinetic energy were along curvilinear paths. Our findings demonstrate that participants were capable of finding the energy-optimal paths, but only when provided with veridical visual and haptic information pertaining to the object, lacking which the trajectories were executed along rectilinear paths.

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<![CDATA[Chemomechanical regulation of myosin Ic cross-bridges: Deducing the elastic properties of an ensemble from single-molecule mechanisms]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be023c

Myosin Ic is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by hair cells, the sensory receptors of the inner ear. In this context myosin molecules operate neither as filaments, as occurs in muscles, nor as single or few molecules, as characterizes intracellular transport. Instead, myosin Ic molecules occur in a complex cluster in which they may exhibit cooperative properties. To better understand the motor’s remarkable function, we introduce a theoretical description of myosin Ic’s chemomechanical cycle based on experimental data from recent single-molecule studies. The cycle consists of distinct chemical states that the myosin molecule stochastically occupies. We explicitly calculate the probabilities of the occupancy of these states and show their dependence on the external force, the availability of actin, and the nucleotide concentrations as required by thermodynamic constraints. This analysis highlights that the strong binding of myosin Ic to actin is dominated by the ADP state for small external forces and by the ATP state for large forces. Our approach shows how specific parameter values of the chemomechanical cycle for myosin Ic result in behaviors distinct from those of other members of the myosin family. Integrating this single-molecule cycle into a simplified ensemble description, we predict that the average number of bound myosin heads is regulated by the external force and nucleotide concentrations. The elastic properties of such an ensemble are determined by the average number of myosin cross-bridges. Changing the binding probabilities and myosin’s stiffness under a constant force results in a mechanical relaxation which is large enough to account for fast adaptation in hair cells.

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