Simulating contact using the elastic foundation algorithm in OpenSim

Modeling joint contact in OpenSim is not well understood. This study systematically investigated the variables associated with the elastic foundation contact model within OpenSim by performing a series of controlled benchtop experiment and concomitant simulations. Four metal-on-plastic interactions were modeled, including a model of a total knee replacement (TKR). Load-displacement curves were recorded during cyclic loading between 100 and 750 N. Geometries were imported and into OpenSim and contact mechanics were modeled with the on-board elastic foundation algorithm. A hybrid optimization algorithm determined that stiffness and dissipation coefficients for TKR implants were 1.52 × 10¹⁰ N/m and 57.7 Ns/m, respectively. Estimations of contact forces were 10.2% of blinded experimental data (average root mean square error: 76.82 ± 11.47 N). In the second portion of this study, freely available eTibia TKR renderings were used to test the ubiquity of the tuning parameters. They were also used to perform a sensitivity analysis of material stiffness and mesh density with regard to penetration depth and computational time. When a stiffness of 1 × 10¹⁰ was applied to an eTibia model with 5000 faces, a 100 kg load caused 0.259 mm of penetration. Under the same conditions, the tuned model experienced 0.300 mm of penetration. Material stiffnesses between 1 × 10¹³ and 1 × 10¹⁵ N/m increased computation time by factors of 12–23. This study provides much needed clarity regarding the use of the OpenSim EF algorithm. It also demonstrates the utility of OpenSim to model deformable materials and complex geometries, and this approach can be adapted to make reasonable estimations for both natural and surgically modified joints.     

The interaction and fusion of bilayers formed from unsaturated lipids

The interactions between unsaturated phospholipid bilayers deposited on mica were measured in aqueous solution using a surface forces apparatus. The bilayers were made of L--dioleoylphosphatidylcholine (DOPC), L--dioleoylphosphatidyl ethanolamine (DOPE), and mixtures of the two, and were formed on mica by Langmuir-Blodgett deposition after the lipids were spread on an aqueous substrate from a chloroform solution. The forces are interpreted as electrostatic double-layer and van der Waals forces with long range, and a strong repulsion (hydration or steric force) at distances of several nm. Together they produce a region of weak attraction (a secondary minimum) at 5 nm (DOPE) and 6 nm (DOPC). Fusion of two bilayers into one was observed when the local force per unit area was 2–3 MPa. Other researchers report that phosphatidylethanolamine in vesicles enhances fusion. In this study using deposited bilayers, the presence of DOPE in a DOPC bilayer did not promote fusion, nor did DOPE bilayers fuse more easily than DOPC. The value of the force per unit area at which the two bilayers fuse into one was however decreased by several orders of magnitude when the bilayers were formed from lipids kept in chloroform solution for several days or more. Chromatography showed traces of lipid degradation products in such chloroform solutions.Abbreviations DO dioleoyl- - PE phosphatidyl ethanolamine - PC phosphatidylcholine - FECO fringes of equal chromatic order Of fprint requests to: J. Wolfe     

Seed-breaking forces exerted by orang-utans with their teeth in captivity and a new technique for estimating forces produced in the Wild

Orang-utans (Pongo pygmaeus) at the Singapore Zoological Gardens were presented with two thick-shelled edible seeds, Mezzettia parviflora (Annonaceae) and Macadamia ternifolia (Proteaceae) in order to estimate their maximum bite forces. The orang-utans could break the Macadamia seeds in one bite, while those of Mezzettia required repeated attempts. Examination of shell fragments showed that many had scratches and some had clear, but small (ca. 1–2 mm diameter), impressions on them. Building upon this information, semi-imitative tests were performed on the seeds in a universal testing machine by loading them in compression with either flat plates or metal casts of orang-utan cheek teeth. The maximum forces required to break the seeds were similar with both the flat plates and the metal teeth; the average for the Macadamia seeds being about 2,000 N (which forms a minimum estimate for the maximum bite forces in orang-utans) and for the Mezzettia seeds, 6,000 N. The work done with the metal teeth was much greater than with the plates. A mechanical analysis showed that this extra work went into producing permanent impressions (“bite marks”) in the shell with the tooth cusps. These impressions were larger than those found on the shells of seeds bitten by the orang-utans. Nevertheless, it is shown theoretically that the size of these indentations can give an estimate of the bite forces used. The maximum force developed in the machine tests with the metal teeth was correlated with the force calculated from analysis of the bite marks. The method is suitable for use in field studies where the marks left on remnants of hard foods eaten by primates may be used to estimate, very roughly, the forces used to produce them. © 1994 Wiley-Liss, Inc.     

Understanding force-generating microtubule systems through in vitro reconstitution

ABSTRACT

Microtubules switch between growing and shrinking states, a feature known as dynamic instability. The biochemical parameters underlying dynamic instability are modulated by a wide variety of microtubule-associated proteins that enable the strict control of microtubule dynamics in cells. The forces generated by controlled growth and shrinkage of microtubules drive a large range of processes, including organelle positioning, mitotic spindle assembly, and chromosome segregation. In the past decade, our understanding of microtubule dynamics and microtubule force generation has progressed significantly. Here, we review the microtubule-intrinsic process of dynamic instability, the effect of external factors on this process, and how the resulting forces act on various biological systems. Recently, reconstitution-based approaches have strongly benefited from extensive biochemical and biophysical characterization of individual components that are involved in regulating or transmitting microtubule-driven forces. We will focus on the current state of reconstituting increasingly complex biological systems and provide new directions for future developments.     

Coulomb Forces and Potentials in Systems with an Orthorhombic Unit Cell

Abstract

R. Sperb's development of the author's earlier work on summation of Coulomb fields in periodically repeated systems with a cubic unit cell is extended to systems with an orthorhombic unit cell. This permits rapid evaluation of Coulomb forces and potentials in systems other than those with a cubic unit cell. A general formula enables the Madelung constant to be calculated, as a function of the cell dimensions a, b and c.     

Comparison of an EMG-based and a stress-based method to predict shoulder muscle forces

The estimation of muscle forces in musculoskeletal shoulder models is still controversial. Two different methods are widely used to solve the indeterminacy of the system: electromyography (EMG)-based methods and stress-based methods. The goal of this work was to evaluate the influence of these two methods on the prediction of muscle forces, glenohumeral load and joint stability after total shoulder arthroplasty. An EMG-based and a stress-based method were implemented into the same musculoskeletal shoulder model. The model replicated the glenohumeral joint after total shoulder arthroplasty. It contained the scapula, the humerus, the joint prosthesis, the rotator cuff muscles supraspinatus, subscapularis and infraspinatus and the middle, anterior and posterior deltoid muscles. A movement of abduction was simulated in the plane of the scapula. The EMG-based method replicated muscular activity of experimentally measured EMG. The stress-based method minimised a cost function based on muscle stresses. We compared muscle forces, joint reaction force, articular contact pressure and translation of the humeral head. The stress-based method predicted a lower force of the rotator cuff muscles. This was partly counter-balanced by a higher force of the middle part of the deltoid muscle. As a consequence, the stress-based method predicted a lower joint load (16% reduced) and a higher superior–inferior translation of the humeral head (increased by 1.2 mm). The EMG-based method has the advantage of replicating the observed cocontraction of stabilising muscles of the rotator cuff. This method is, however, limited to available EMG measurements. The stress-based method has thus an advantage of flexibility, but may overestimate glenohumeral subluxation.     

Cold and Warm Denaturation of Proteins

We introduce a simplified protein model where the water degrees of freedom appear explicitly (although in an extremely simplified fashion). Using thismodel we are able to recover both the warm and the cold protein denaturation within a single framework, while addressing important issues about the structure of model proteins.     

Stretching Micropatterned Cells on a PDMS Membrane

Mechanical forces exerted on cells and/or tissues play a major role in numerous processes. We have developed a device to stretch cells plated on a PolyDiMethylSiloxane (PDMS) membrane, compatible with imaging. This technique is reproducible and versatile. The PDMS membrane can be micropatterned in order to confine cells or tissues to a specific geometry. The first step is to print micropatterns onto the PDMS membrane with a deep UV technique. The PDMS membrane is then mounted on a mechanical stretcher. A chamber is bound on top of the membrane with biocompatible grease to allow gliding during the stretch. The cells are seeded and allowed to spread for several hours on the micropatterns. The sample can be stretched and unstretched multiple times with the use of a micrometric screw. It takes less than a minute to apply the stretch to its full extent (around 30%). The technique presented here does not include a motorized device, which is necessary for applying repeated stretch cycles quickly and/or computer controlled stretching, but this can be implemented. Stretching of cells or tissue can be of interest for questions related to cell forces, cell response to mechanical stress or tissue morphogenesis. This video presentation will show how to avoid typical problems that might arise when doing this type of seemingly simple experiment.     

Effects of femoral component placement on the balancing of a total knee at surgery

Misalignment and soft-tissue imbalance in total knee arthroplasty (TKA) can cause discomfort, pain, inadequate motion and instability that may require revision surgery. Balancing can be defined as equal collateral ligament tensions or equal medial and lateral compartmental forces during the flexion range. Our goal was to study the effects on balancing of linear femoral component misplacements (proximal, distal, anterior, posterior); and different component rotations in mechanical alignment compared to kinematic alignment throughout the flexion path. A test rig was constructed such that the position of a standard femoral component could be adjusted to simulate the linear and rotational positions. With the knee in neutral reference values of the collateral tensions were adjusted to give anatomic contact force patterns, measured with an instrumented tibial trial. The deviations in the forces for each femoral component position were then determined. Compartmental forces were significantly influenced by 2 mm linear errors in the femoral component placement. However, the errors were least for a distal error, equivalent to undercutting the distal femur. The largest errors mainly increase the lateral condyle force, occurred for proximal and posterior component errors. There were only small contact force differences between kinematic and mechanical alignment. Based on these results, surgeons should avoid overcutting the distal femur and undercutting the posterior femur. However, the 2–3 degrees varus slope of the joint line as in kinematic alignment did not have much effect on balancing, so mechanical or kinematic alignment were equivalent.     

The application of musculoskeletal modeling to investigate gender bias in non-contact ACL injury rate during single-leg landings

The central tenet of this study was to develop, validate and apply various individualised 3D musculoskeletal models of the human body for application to single-leg landings over increasing vertical heights and horizontal distances. While contributing to an understanding of whether gender differences explain the higher rate of non-contact anterior cruciate ligament (ACL) injuries among females, this study also correlated various musculoskeletal variables significantly impacted by gender, height and/or distance and their interactions with two ACL injury-risk predictor variables; peak vertical ground reaction force (VGRF) and peak proximal tibia anterior shear force (PTASF). Kinematic, kinetic and electromyography data of three male and three female subjects were measured. Results revealed no significant gender differences in the musculoskeletal variables tested except peak VGRF (p = 0.039) and hip axial compressive force (p = 0.032). The quadriceps and the gastrocnemius muscle forces had significant correlations with peak PTASF (r = 0.85, p < 0.05 and r = ? 0.88, p < 0.05, respectively). Furthermore, hamstring muscle force was significantly correlated with peak VGRF (r = ? 0.90, p < 0.05). The ankle flexion angle was significantly correlated with peak PTASF (r = ? 0.82, p < 0.05). Our findings indicate that compared to males, females did not exhibit significantly different muscle forces, or ankle, knee and hip flexion angles during single-leg landings that would explain the gender bias in non-contact ACL injury rate. Our results also suggest that higher quadriceps muscle force increases the risk, while higher hamstring and gastrocnemius muscle forces as well as ankle flexion angle reduce the risk of non-contact ACL injury.     

Amyloid from a histochemical perspective. A review of the structure,properties and types of amyloid,and a proposed staining mechanism for Congo red staining

Amyloid is a diverse group of unrelated peptides or proteins that have positive functionality or are associated with various pathologies. Despite vast differences, all amyloids share several features that together uniquely define the group. 1) All amyloids possess a characteristic cross-ß pattern with X-ray diffraction typical of ß-sheet secondary protein structures. 2) All amyloids are birefringent and dichroic under polarizing microscopy after staining with Congo red, which indicates a crystalline-like (ordered) structure. 3) All amyloids cause a spectral shift in the peak wavelength of Congo red with conventional light microscopy due to perturbation of π electrons of the dye. 4) All amyloids show heightened intensity of fluorescence with Congo red, which suggests an unusual degree of packing of the dye onto the substrate. The ß portion of amyloid molecules, the only logical substrate for specific Congo red staining under histochemical conditions, consists of a stack of ß-sheets laminated by hydrophilic and hydrophobic interactions between adjacent pairs. Only the first and last ß-sheets are accessible to dyes. Each sheet is composed of numerous identical peptides running across the width of the sheet and arranged in parallel with side chains in register over the length of the fibril. Two sets of grooves are bordered by side chains. X grooves run perpendicular to the long axis of the fibril; these grooves are short (the width of the sheet) and number in the hundreds or thousands. Y grooves are parallel with the long axis. Each groove runs the entire length of the fibril, but there are very few of them. While Congo red is capable of ionic bonding with proteins via two sulfonic acid groups, physical constraints on the staining solution preclude ionic interactions. Hydrogen bonding between dye amine groups and peptide carbonyls is the most likely primary bonding mechanism, because all ß-sheets possess backbone carbonyls. Various amino acid residues may form secondary bonds to the dye via any of three van der Waals forces. It is possible that Congo red binds within the Y grooves, but that would not produce the characteristic staining features that are the diagnostic hallmarks of amyloid. Binding in the X grooves would produce a tightly packed series of dye molecules over the entire length of the fibril. This would account for the signature staining of amyloid by Congo red: dichroic birefringence, enhanced intensity of fluorescence and a shift in visible absorption wavelength.     

Regulation of boreal forest understory vegetation: the roles of resources and herbivores

To understand inter-trophic linkages between components of the boreal forest understory vegetation, three hypotheses were tested: survival, growth and abundance of grasses and legumes were controlled by (i) resource availability alone, (ii) by herbivores alone, and (iii) by both resource availability and herbivores. The hypotheses were tested using three experimental treatments – fertilization, herbivore exclusion, and fertilization plus herbivore exclusion – in three areas having different densities of resident herbivores, mostly snowshoe hares and ground squirrels. The highest density of snowshoe hares is comparable to natural levels during peaks in the snowshoe hare cycle. As the density of herbivores increased so too did the level of response by the measured variables – survival, growth of transplants and leaf area index of established vegetation. In general, fertilization resulted in a decrease in survival and growth of transplants, and fences increased survival and growth; both responses were more noticeable at higher herbivore densities. Fertilizer and herbivore exclosure fences had only negligible effects on established grass and legume abundance at all hare densities. We have shown that some hypotheses of vegetation regulation are over-simplified because different species groups (i.e., grasses and legumes) are regulated by different factors, at different life history stages, and sometimes these factors act in opposing directions. We argue that during the increase phase and peak of the snowshoe hare cycle (high herbivore density), growth and survival of establishing plants is regulated by herbivores. During the decline and low phases of the snowshoe hare cycle herbivores will have little impact on early life stages, whereas the established, mature, vegetation will be resource-regulated. Because of the variability in responses to the same manipulations we may begin to understand which plant life history stages are most vulnerable to consumer and resource regulation, the magnitudes of these sources of regulation at each of these stages, and how these vary among species groups and types of environments.     

Relation between subject-specific hip joint loading, stress distribution in the proximal femur and bone mineral density changes after total hip replacement

In the prediction of bone remodelling processes after total hip replacement (THR), modelling of the subject-specific geometry is now state-of-the-art. In this study, we demonstrate that inclusion of subject-specific loading conditions drastically influences the calculated stress distribution, and hence influences the correlation between calculated stress distributions and changes in bone mineral density (BMD) after THR.For two patients who received cementless THR, personalized finite element (FE) models of the proximal femur were generated representing the pre- and post-operative geometry. FE analyses were performed by imposing subject-specific three-dimensional hip joint contact forces as well as muscle forces calculated based on gait analysis data. Average values of the von Mises stress were calculated for relevant zones of the proximal femur. Subsequently, the load cases were interchanged and the effect on the stress distribution was evaluated. Finally, the subject-specific stress distribution was correlated to the changes in BMD at 3 and 6 months after THR.We found subject-specific differences in the stress distribution induced by specific loading conditions, as interchanging of the loading also interchanged the patterns of the stress distribution. The correlation between the calculated stress distribution and the changes in BMD were affected by the two-dimensional nature of the BMD measurement.Our results confirm the hypothesis that inclusion of subject-specific hip contact forces and muscle forces drastically influences the stress distribution in the proximal femur. In addition to patient-specific geometry, inclusion of patient-specific loading is, therefore, essential to obtain accurate input for the analysis of stress distribution after THR.     

Laser-guided direct writing for three-dimensional tissue engineering

One of the principal limitations to the size of an engineered tissue is oxygen and nutrient transport. Lacking a vascular bed, cells embedded in an engineered tissue will consume all available oxygen within hours while out branching blood vessels will take days to vascularize the implanted tissue. One possible solution is to directly write vascular structures within the engineered tissue prior to implantation, reconstructing the tissue according to its native architecture. The cell patterning technique, laser-guided direct writing (LGDW), can pattern multiple cells types with micrometer resolution on arbitrary surfaces, including biological gels. Here we show that LGDW can pattern human umbilical vein endothelial cells (HUVEC) in two- and three-dimensions with micrometer accuracy. By patterning HUVEC on Matrigel, we can direct their self-assembly into vascular structures along the desired pattern. Finally, co-culturing the vascular structures with hepatocytes resulted in an aggregated tubular structure similar in organization to a hepatic sinusoid. This capability can facilitate studies of tissue architecture at the single cell level, and of heterotypic interactions underlying processes such as liver and pancreas morphogenesis, differentiation, and angiogenesis.     

Musculoskeletal model choice influences hip joint load estimations during gait

The prevalence of musculoskeletal modeling studies investigating hip contact forces and the number of models used to conduct such investigations has increased in recent years. However, the consistency between models remain unknown and differences in model predicted hip contact forces between studies are difficult to distinguish from natural inter-individual differences. The purpose of this study was therefore to evaluate differences in hip joint contact forces during gait between four OpenSim models. These models included the generic models gait2392 and the Arnold Lower Limb Model, as well as the hip specific models hip2372 and London Lower Limb Model. Data from four individuals who have had a total hip replacement with instrumented hip implants performing slow, normal, and fast walking trials were taken from the HIP98 database to evaluate the various models effectiveness at estimating hip loads. Muscle forces were estimated using static optimization and hip contact forces were calculated using the JointReaction analysis in OpenSim. Results indicated that, for gait, the hip specific London Lower Limb Model consistently predicted peak push-off hip joint contact forces with lower magnitude and timing errors compared to the other models. Likewise, root mean square error values were lowest and correlation coefficients were highest for the London Lower Limb Model. These results suggest that the London Lower Limb Model is the most appropriate model for investigations focused on hip joint loading.     

Muscle contraction: viscous-like frictional forces and the impulsive model

Apart from a few experimental studies muscle viscosity has not received much recent analytical attention as a determinant of the contractile process. This is surprising, since any muscle cell is 80% water, and may undergo large shape changes during its working cycle. Intuitively one might expect the viscosity of the solvent to be an important determinant of the physiological activity of muscle tissue. This was apparent to pioneers of the study of muscle contraction such as Hill and his contemporaries, whose putative theoretical formulations contained terms related to muscle viscosity. More recently, though, a hydrodynamic calculation by Huxley, using a solvent viscosity close to that of water, has been held to demonstrate that viscous forces are negligible in muscle contraction. We have re-examined the role of viscosity in contraction, postulating impulsive acto-myosin forces that are opposed by a viscous resistance between the filaments. The viscous force required, 10⁴ times the hydrodynamic estimate, is close to recent experimental measurements, themselves 10²–10³ times the hydrodynamic estimate. This also agrees with contemporary measurements of cytoplasmic viscosity in other biological cells using magnetic bead micro-rheometry. These are several orders of magnitude greater than the viscosity of water. In the course of the analysis we have derived the force-velocity equation for an isolated half-sarcomere containing a single actin filament for the first time, and from first principles. We conclude that muscle viscosity is indeed important for the contractile process, and that it has been too readily discounted.