The Achilles tendon is the thickest tendon in the human body, and it is composed of three subtendons connected to the calf muscles (soleus, medial and lateral gastrocnemius). This study aimed to evaluate the importance of explicitly modeling subtendons and collagen fiber orientation on the predicted strain distribution within tendon tissue during mechanical loading. Magnetic resonance images from seven subjects were used to create subject-specific finite element models. The segmented tendons were modeled in two ways: the entire tendon as one structure, then dividing it into the three subtendons. A fiber-reinforced poro-visco-hyperelastic material model was used to describe the mechanical response. The collagen fibers were first oriented in the proximal–distal direction, then twisted following the subtendon orientation. Principal strains were analyzed, assessing the impact of subject-specific geometry on strain magnitudes, localization and distributions. Average strains were similar across subjects (coefficient of variation = 18
To develop a fully coupled, patient-specific fluid–structure interaction (FSI) framework for quantitative assessment of post–transcatheter aortic valve implantation (TAVI) hemodynamics and valve biomechanics, and to compare selected simulation-derived hemodynamic indices with post-procedural echocardiographic measurements. Patient-specific geometries were reconstructed from pre-operative computed tomography angiography in five subjects treated with SAPIEN 3 Ultra (S3) devices. Structural TAVI deployment was simulated using Abaqus/Explicit and subsequently coupled with FlowVision for performing a two-way post-TAVI FSI analysis. Personalized boundary conditions were derived from clinical measurements, including heart rate, blood pressure, and echocardiographic flow data. Predicted peak velocity, effective orifice area (EOA), and transvalvular pressure gradients (TPG) were quantitatively compared with post-procedural echocardiography using empirical cumulative distribution functions and area-based error metrics. The FSI framework reproduced realistic leaflet kinematics and patient-specific flow patterns, highlighting marked inter-patient variability despite identical device types. Average of predicted peak systolic velocity (2.66 ± 0.59 m/s) and TPG (22 ± 10.7 mmHg) showed good agreement with echocardiographic measurements as the area metric was below 10
Premature ventricular complexes (PVCs) are common cardiac arrhythmias that can lead to cardiomyopathy when frequent. Post-extrasystolic potentiation (PESP), which is the transient increase in contractility following a PVC, may serve as a predictive marker for heart failure risk; yet, the underlying calcium-mediated mechanisms and their relative contribution compared to loading conditions remain poorly understood. We integrated a mechanochemical model coupling intracellular calcium dynamics to sarcomere mechanics within the CircAdapt closed-loop cardiovascular framework. A novel calcium source model incorporating the force–interval relationship was calibrated using experimental canine data. We simulated single PVCs across varying coupling intervals and systematically investigated the contributions of calcium dynamics versus loading conditions to PESP, quantified as changes in systolic blood pressure (∆SBP), maximum rate of left ventricular pressure rise (∆max(dPLv/dt)), and left ventricular ejection fraction (∆LVEF). The calcium-based force–interval relationship reproduced experimental mechanical restitution curves with high accuracy (RMSE 9.59 ± 0.08
Finite element (FE) models are used to study spinal cord biomechanics and injury mechanisms. However, most existing models incorporate full vertebral geometry, substantially increasing computational cost and limiting the ability to perform large-scale parametric studies or apply modeling in clinically feasible timelines. In central cord syndrome, movement of the vertebrae is important while vertebral deformation contributes minimally to cord biomechanics. This study tested whether modeling the spinal canal geometry alone (versus full vertebral geometry) is sufficient to capture spinal cord stresses and strains under extension loading, offering a computationally efficient alternative to high-fidelity subject-specific models. Two FE models were developed: (1) a high-fidelity model including vertebrae, discs, ligaments, and neurological tissues, and (2) a computationally efficient (CE) model retaining only the spinal canal, with boundary conditions applied to represent the kinematics of each vertebra. Tissue-level stress and strain distributions, and computational performance were evaluated under extension. The CE model reproduced whole-cord and tissue-level stresses within 15
Intimal hyperplasia is a pathological mechanism underlying arterial growth and remodeling in numerous vascular diseases, in which key biological processes are regulated by mechanical fields such as wall shear stress (WSS) and circumferential stress within the artery walls. In the present study, we hypothesize that chronic exposure to hand-arm vibrations (HAV) contributes to the development of intimal hyperplasia in the digital artery through vibration-induced reductions in WSS. Accordingly, a mechanobiological framework coupling an agent-based model (ABM) with a finite element model (FEM) was developed. The ABM captures the hemodynamics-driven and mechanoregulated cellular and molecular mechanisms involved in this pathology, including mediator secretion by endothelial and smooth muscle cells (SMCs), SMCs proliferation and migration, and extracellular matrix (ECM) synthesis and degradation. WSS values, reflecting the presence or absence of vibration during long-term working conditions, were used as model inputs. Circumferential stresses were computed using the FEM, which describes the mechanical behavior of the digital artery. The model parameters were identified from our experimental findings and literature data. Over a 5 year period of vibration exposure (4 h/day), our simulations revealed that the constitutive law of the arterial walls had a negligible impact on the progression of stenosis. Moreover, reductions in circumferential stress associated with arterial wall thickening led to ECM degradation in the media layer due to an increase in the production of matrix metalloproteinase-2. This mechanobiological framework provides a computational tool for estimating vibration-induced stenosis rates and can be extended to study intimal hyperplasia in diverse biomechanical and pathological contexts.
Existing in vitro and numerical studies lack consensus regarding whether and how coronary arteries should be incorporated. This study aims to systematically investigate the effects of coronary artery outlets on the hemodynamic environment within the native sinus and neo-sinus after transcatheter aortic valve implantation (TAVI). Three idealized aortic root models (without coronaries, single coronary, and bilateral coronaries) were fabricated. A VENUS self-expanding valve was implanted at five depths (0 mm, ± 5 mm and ± 10 mm). A pulsatile in vitro flow platform combined with particle image velocimetry (PIV) was applied to quantify velocity fields, vorticity, and particle washout. Correlations between implantation depth and hemodynamic parameters were further assessed. In control models, mean native sinus velocity without coronaries was 0.58 ± 0.49 cm/s and decreased further after TAVI. Introducing a single coronary increased mean velocity to 1.34 ± 0.95 cm/s and generated high-velocity jets (> 10 cm/s) near the ostium; bilateral coronaries produced comparable effects. Vorticity decreased in all post-TAVI configurations. Particle washout analysis demonstrated pronounced stasis without coronary flow but markedly improved clearance when coronary inflow was present. With coronary flow, particle washout was markedly enhanced compared with the no-coronary condition, but did not vary monotonically with implantation depth; instead, it appeared to be governed by the combined effects of local flow environment. Under the present conditions, coronary flow substantially increased velocity magnitude, vorticity, and particle washout within the corresponding native sinus and neo-sinus after self-expanding valve implantation. Neglecting coronary outlets may lead to a substantial underestimation of sinus flow velocity and washout. However, when evaluating the hemodynamics of an individual coronary sinus, inclusion of its corresponding coronary artery alone is likely to be sufficient to capture the essential flow characteristics.
The aim of this study was to evaluate StepAn as an automated approach for quantitative gait analysis in rodents. We sought to determine whether this video-based approach, which uses standard recordings from devices like smartphones, could sensitively detect motor deficits in a pharmacological model of Parkinsonian bradykinesia. Wistar rats received a single intraperitoneal injection of saline (control), 0.15 mg/kg haloperidol, or 0.30 mg/kg haloperidol. One hour post-injection, gait was analyzed using both the traditional manual “Footprints” test and the StepAn-based automated video analysis, which performs paw detection and stride length calculation from video recordings. Both analysis methods detected a significant reduction in average stride length in haloperidol-treated rats compared to controls (p<0.001), confirming the expected bradykinetic phenotype. No significant difference was found between the two haloperidol doses. Automated analysis provided equivalent mean values but demonstrated superior precision, evidenced by significantly lower measurement variability compared to manual scoring. We evaluated StepAn as a precise and hardware-flexible tool for quantitative gait assessment. Its ability to detect drug-induced Parkinsonian gait deficits comparable to established methods supports its use for objective locomotor analysis in preclinical research.
KRAS is a small GTPase essential for cell signaling, and the G12C mutation acts as a key oncogenic driver in multiple cancers. First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, have shown clinical efficacy, but are limited by acquired resistance due to secondary mutations. In this study, we investigated the impact of secondary mutations (Y96D, Y96S, G13D, and Q99L) on the binding efficacy of sotorasib, adagrasib, and the next-generation inhibitor (MK-1084) using molecular dynamics simulations, binding free energy calculations, and dynamic protein-ligand interaction analysis. Our study revealed that each secondary mutant variant exhibited variations in the degree of resistance to the inhibitors. Two major resistance patterns were identified: direct and indirect. Our analyses revealed that Y96 mutations directly disrupt inhibitor binding, conferring high resistance to all three inhibitors, whereas G13D and Q99L indirectly alter the binding environment by influencing other residues, resulting in variable resistance profiles. This study provides detailed molecular insights into resistance mechanisms to support the rational design of more robust KRAS G12C-targeted therapies.
Bioluminescence is an oxidation-mediated chemical reaction involving the luciferase enzyme and the luciferin substrate. To date, various artificial luciferases have been developed, and their luminescence properties have been investigated. However, very few studies have focused on the solvent environment in which these luminescent reactions occur, and the details of their influence on luminescent phenomena remain unclear. In this study, we investigated the effects of various surfactants on the activity of the luciferase picALuc. To this end, we analyzed the effects of adding diverse surfactants on the luminescence properties of the luciferase picALuc. The results showed that the addition of a surfactant enhanced the luminescence intensity and extended the duration of luminescence. Dynamic light scattering measurements and microscopic observations revealed that micelle-like particles were formed by the surfactant, which suppressed luminescence inhibition. This study provides our original method for adding surfactants to enzymatic reactions, such as those involving hydrophobic substrates.
The sacroiliac joints (SIJs) and pubic symphysis (PS) form a ‘pelvic ring’ that plays a critical role in load transfer between the spine and lower extremities. Direct in vivo measurement of pelvic joint loading remains challenging, and existing musculoskeletal models often simplify or exclude pubic joint contributions. This study developed a female pelvis musculoskeletal model incorporating both SIJs and PS, integrated with a personalisation framework including: (1) a pelvis shape-scaling workflow based on a female statistical shape model; and (2) an inertia estimation workflow using 3D full-body scans. Kinematic and kinetic data were collected from eight healthy female participants during bilateral standing, single-leg standing and walking. Compressive and superior–inferior shear loads at the SIJs and PS were estimated using inverse dynamics and static optimisation. The model produced physiologically plausible joint loads consistent with previous studies. During bilateral standing, pubic joint loads were minimal, and SIJ loads showed minor asymmetries. Single-leg standing induced SIJ tensile (1.9 N/kg), pubic compression (2.2 N/kg), and superior–inferior shearing at the support-side SIJ (4 N/kg). During walking, pubic joint loads were closely related to SIJ loading patterns and appeared to facilitate load transmission from the stance-side SIJ to the swing-side SIJ. This pelvis musculoskeletal model provides a feasible tool for investigating SIJ and PS reaction forces in females, enabling a more physiologically realistic assessment of pelvic joint biomechanics than previously available models. The proposed framework is adaptable to other populations and supports future research on pelvic pain mechanisms, pregnancy-related adaptations, and sex-specific musculoskeletal disorders.
Right ventricular (RV) dysfunction due to pulmonary and tricuspid valve regurgitation remains understudied despite its critical role in adverse cardiac outcomes. We present a biventricular computational model that integrates regurgitant valves in the RV with a kinematic growth framework. Updated reference configurations are used to allow saturated growth in each growth cycle. Acute regurgitation scenarios and long-term adaptation are modelled to quantify structural and functional adaptations in the RV and their further impacts on left ventricular (LV) performance. Results demonstrate that persistent regurgitation drives dominant eccentric growth in the RV, leading to severe cavity dilation, septal displacement, and impaired LV filling and systolic function. Simulations incorporating both eccentric and concentric growth reveal a limited compensatory role for concentric thickening, even under severe volume overload. The simulated haemodynamic and functional responses are broadly consistent with clinical observations and capture clinically plausible trajectories of RV growth under sustained regurgitation. These findings suggest that biomechanical modelling of myocardial adaptation could provide mechanistic insights into RV adaptation under severe valve regurgitation, and may support clinical decision-making regarding RV failure once fully validated. Future work should focus on validating myocardial growth laws using experimental and clinical data, and extending the framework to patient-specific scenarios for predictive modelling of RV dysfunction due to valve regurgitation.
Hyperthermal sarcomeric oscillations (HSOs) expose rapid sarcomere-level motion in living cardiomyocytes and provide a mesoscopic window between actomyosin activity and robust cellular contraction. I reanalyzed high-speed sarcomere-length recordings from five consecutive sarcomeres in each of seven neonatal rat cardiomyocytes. During HSOs, local phase relations became trackable through most of the oscillatory segment (valid fraction, 0.298 before warming and 0.956 during HSOs; paired Wilcoxon P=0.0156). Neighboring-sarcomere reconfiguration was dominated by one-link switches, in which one adjacent-pair relation changed while the other three were maintained (216/230 HSO phase transitions), and anti-phase-rich occupancy increased from 0.254 to 0.509 (P=0.0156). I then measured event-local relative internal length redistribution. For each reach-qualified one-link event, compensation reach, S, was defined as the expected sarcomere-index distance between relative shortening and relative lengthening. The same directed IAAI-to-IAII switch was accompanied by short-reach redistribution in one event (S=1.29) and cross-chain redistribution in another (S=2.88). Across 248 reach-qualified events, S increased with the pre-event number of I-type links, with a cell-fixed slope of 0.148 span units per added I-link supported by cell-blocked permutation and cell-cluster bootstrap analyses. Thus, HSO reveals a mesoscale organizing process in which a local switch in neighboring-sarcomere synchrony is linked to spatially distributed relative internal length redistribution whose reach is shaped by the pre-event phase context.
Aortic dissection is a life-threatening pathology characterized by the progressive delamination of adjacent lamellar units within the aortic media. Because this internal damage propagates predominantly along the radial direction of the arterial wall, radial tensile testing has emerged as a particularly relevant experimental configuration to reproduce the mechanical conditions associated with dissection. Several experimental studies have reported the mechanical response of arterial tissues under radial tension, highlighting pronounced viscoelasticity, fluid-driven effects, and progressive damage. However, despite these advances, a coherent constitutive framework capable of reproducing the full mechanical response of arterial tissue subjected to radial tensile loading is still lacking. In this study, we propose a computational model specifically designed to describe arterial tissue behavior under radial tensile testing. The model combines a biphasic formulation, accounting for fluid–solid interactions, with a reactive viscoelastic damage framework to capture time-dependent response and progressive mechanical degradation. Implemented within the FEBio environment, the model is calibrated using experimental radial tensile tests on aortic tissue. The proposed formulation accurately reproduces key experimental features, including stress relaxation, nonlinear stiffening, and damage progression. These results demonstrate that the model provides a physically consistent description of arterial tissue behavior under radial tension and represents a relevant tool for investigating the mechanical mechanisms preceding aortic dissection.
