Generation of propulsive force via vertical undulations in snakes.
Ontology highlight
ABSTRACT:
SUBMITTER: Jurestovsky DJ
PROVIDER: S-EPMC8278011 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Before succumbing to slower speeds, older adults may walk with a diminished push-off to prioritize stability over mobility. However, direct evidence for trade-offs between push-off intensity and balance control in human walking, independent of changes in speed, has remained elusive. As a critical first step, we conducted two experiments to investigate: (i) the independent effects of walking speed and propulsive force (FP) generation on dynamic stability in young adults, and (ii) the extent to which young adults prioritize dynamic stability in selecting their preferred combination of walking speed and FP generation. Subjects walked on a force-measuring treadmill across a range of speeds as well as at constant speeds while modulating their FP according to a visual biofeedback paradigm based on real-time force measurements. In contrast to improvements when walking slower, walking with a diminished push-off worsened dynamic stability by up to 32%. Rather, we find that young adults adopt an FP at their preferred walking speed that maximizes dynamic stability. One implication of these findings is that the onset of a diminished push-off in old age may independently contribute to poorer balance control and precipitate slower walking speeds.
| S-EPMC5717707 | biostudies-literature
Project description:Does cytosolic pressure facilitate f-actin polymerization to push the leading edge of a cell forward during self-propelled motion? AFM force-distance (f-d) curves obtained from lamellipodia of live cells often exhibit a signal from which the tension, bending modulus, elastic modulus and thickness in the membrane-cortex complex can be estimated close to the contact point. These measurements permit an estimate of the cytosolic pressure via the canonical Laplace force balance. The deeper portion of the f-d curve allows estimation of the bulk modulus of the cytoskeleton after removal of the bottom effect artifact. These estimates of tension, pressure, cortex thickness and elastic moduli imply that cytosolic pressure both pushes the membrane forward and compresses the actin cortex rearward to facilitate f-actin polymerization. We also estimate that cytosolic pressure fluctuations, most likely induced by myosin, provide a propulsive force comparable to that provided by f-actin polymerization in a lamellipod.
| S-EPMC4650671 | biostudies-other
Project description:Since the early clinical studies of cancer immunotherapy, the question arose as to whether it was possible to combine it with standard cancer treatments, mostly chemotherapy. The answer, now, is past history. The combined use of immunotherapy and chemotherapy is not only possible but, in certain cases, can be advantageous, depending on the drug, the dose and the combination modalities. In order to find the best synergisms between the two treatments and to turn weak immunotherapeutic interventions into potent anticancer instruments, it is mandatory to understand the complex mechanisms responsible for the positive interactions between chemotherapy and immunotherapy. In this article, we review the current knowledge on mechanisms involved in the immunostimulating activity of chemotherapy and summarize the main studies in both mouse models and patients aimed at exploiting such mechanisms for enhancing the response to cancer immunotherapy.
| S-EPMC5528384 | biostudies-other
Project description:BACKGROUND:Past studies have utilized external interfaces like resistive bands and motor-generated pulling systems to increase limb propulsion during walking on a motorized treadmill. However, assessing changes in limb propulsion against increasing resistance demands during self-controlled walking has not been undertaken. PURPOSE:We assessed limb propulsion against increasing fore-aft loading demands by applying graded fore-aft (FA) resistance at the center of mass during walking in a novel, intent-driven treadmill environment that allowed participants to control their walking speeds. We hypothesized that to maintain a target speed against progressively increasing resistance, participants would proportionately increase their limb propulsion without increasing vertical force production, with accompanying increases in trailing limb angle and positive joint work. METHODS:Seventeen healthy-nonimpaired participants (mean age 52?yrs., SD?=?11) walked at a target, self-controlled speed of 1.0?m/s against 10, 15, 20, and 25% (% body weight) FA resistance levels. We primarily assessed linear slope values across FA resistance levels for mean propulsive force and impulse and vertical impulse of the dominant limb using one-sample t-tests. We further assessed changes in trailing and leading limb angles and joint work using one-way ANOVAs. RESULTS:Participants maintained their target velocity within an a priori defined acceptable range of 1.0?m/s?±?0.2. They significantly increased propulsion proportional to FA resistance (propulsive force mean slope?=?2.45, SD?=?0.7, t (16) =14.44, p?<?0.01; and propulsive impulse mean slope?=?0.7, SD?=?0.25, t (16)?=?11.84, p?<?0.01), but had no changes in vertical impulse (mean slope?=?-?0.04, SD =0.17, p?>?0.05) across FA resistance levels. Mean trailing limb angle increased from 24.3° at 10% resistance to 27.4° at 25% (p?<?0.05); leading limb angle decreased from -?18.4° to -?12.6° (p?<?0.05). We also observed increases in total positive limb work (F (1.7, 26)?=?16.88, p???0.001, ?2?=?0.5), primarily attributed to the hip and ankle joints. CONCLUSIONS:FA resistance applied during self-driven walking resulted in increased propulsive-force output of healthy-nonimpaired individuals with accompanying biomechanical changes that facilitated greater limb propulsion. Future rehabilitation interventions for neurological populations may be able to utilize this principle to design task-specific interventions like progressive strength training and workload manipulation during aerobic training for improving walking function.
| S-EPMC6731616 | biostudies-literature
Project description:Stroke is a leading cause of long-term disability worldwide and often impairs walking ability. To improve recovery of walking function post-stroke, researchers have investigated the use of treatments such as fast functional electrical stimulation (FastFES). During FastFES treatments, individuals post-stroke walk on a treadmill at their fastest comfortable speed while electrical stimulation is delivered to two muscles of the paretic ankle, ideally to improve paretic leg propulsion and toe clearance. However, muscle selection and stimulation timing are currently standardized based on clinical intuition and a one-size-fits-all approach, which may explain in part why some patients respond to FastFES training while others do not. This study explores how personalized neuromusculoskeletal models could potentially be used to enable individual-specific selection of target muscles and stimulation timing to address unique functional limitations of individual patients post-stroke. Treadmill gait data, including EMG, surface marker positions, and ground reactions, were collected from an individual post-stroke who was a non-responder to FastFES treatment. The patient's gait data were used to personalize key aspects of a full-body neuromusculoskeletal walking model, including lower-body joint functional axes, lower-body muscle force generating properties, deformable foot-ground contact properties, and paretic and non-paretic leg neural control properties. The personalized model was utilized within a direct collocation optimal control framework to reproduce the patient's unstimulated treadmill gait data (verification problem) and to generate three stimulated walking predictions that sought to minimize inter-limb propulsive force asymmetry (prediction problems). The three predictions used: (1) Standard muscle selection (gastrocnemius and tibialis anterior) with standard stimulation timing, (2) Standard muscle selection with optimized stimulation timing, and (3) Optimized muscle selection (soleus and semimembranosus) with optimized stimulation timing. Relative to unstimulated walking, the optimal control problems predicted a 41% reduction in propulsive force asymmetry for scenario (1), a 45% reduction for scenario (2), and a 64% reduction for scenario (3), suggesting that non-standard muscle selection may be superior for this patient. Despite these predicted improvements, kinematic symmetry was not noticeably improved for any of the walking predictions. These results suggest that personalized neuromusculoskeletal models may be able to predict personalized FastFES training prescriptions that could improve propulsive force symmetry, though inclusion of kinematic requirements would be necessary to improve kinematic symmetry as well.
| S-EPMC6779709 | biostudies-literature
Project description:Aging elicits numerous effects that impact both musculoskeletal structure and walking function. Tendon stiffness (kT) and push-off propulsive force (FP) both impact the metabolic cost of walking and are diminished by age, yet their interaction has not been studied. We combined experimental and computational approaches to investigate whether age-related changes in function (adopting smaller FP) may be adopted to mitigate the metabolic consequences arising from changes in structure (reduced kT). We recruited 12 young adults and asked them to walk on a force-sensing treadmill while prompting them to change FP (±20% & ±40% of typical) using targeted biofeedback. In models driven by experimental data from each of those conditions, we altered the kT of personalized musculoskeletal models across a physiological range (2-8% strain) and simulated individual-muscle metabolic costs for each kT and FP combination. We found that kT and FP independently affect walking metabolic cost, increasing with higher kT or as participants deviated from their typical FP. Our results show no evidence for an interaction between kT and FP in younger adults walking at fixed speeds. We also reveal complex individual muscle responses to the kT and FP landscape. For example, although total metabolic cost increased by 5% on average with combined reductions in kT and FP, the triceps surae muscles experienced a 7% local cost reduction on average. Our simulations suggest that reducing FP during walking would not mitigate the metabolic consequences of lower kT. Wearable devices and rehabilitative strategies can focus on either kT or FP to reduce age-related increases in walking metabolic cost.
| S-EPMC10602298 | biostudies-literature
Project description:Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (<10 pN), extension fluctuated without resolvable discrete events. In position-clamp experiments, the time-dependent force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H-bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically-coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten-globule states. Monte-Carlo simulations incorporating a compact molten-globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten-globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles.
| S-EPMC5477535 | biostudies-literature
Project description:Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.
| S-EPMC5364437 | biostudies-literature