Myosin-V as a mechanical sensor: an elastic network study

According to recent experiments, the molecular-motor myosin behaves like a strain sensor, exhibiting different functional responses when loads in opposite directions are applied to its tail. Within an elastic-network model, we explore the sensitivity of the protein to the forces acting on the tail and find, in agreement with experiments, that such forces invoke conformational changes that should affect filament binding and ADP release. Furthermore, conformational responses of myosin to the application of forces to individual residues in its principal functional regions are systematically investigated and a detailed sensitivity map of myosin-V is thus obtained. The results suggest that the strain-sensor behavior is involved in the intrinsic operation of this molecular motor.     

A benchtop biorobotic platform for in vitro observation of muscle-tendon dynamics with parallel mechanical assistance from an elastic exoskeleton

We present a novel biorobotic framework comprised of a biological muscle-tendon unit (MTU) mechanically coupled to a feedback controlled robotic environment simulation that mimics in vivo inertial/gravitational loading and mechanical assistance from a parallel elastic exoskeleton. Using this system, we applied select combinations of biological muscle activation (modulated with rate-coded direct neural stimulation) and parallel elastic assistance (applied via closed-loop mechanical environment simulation) hypothesized to mimic human behavior based on previously published modeling studies. These conditions resulted in constant system-level force-length dynamics (i.e., stiffness), reduced biological loads, increased muscle excursion, and constant muscle average positive power output—all consistent with laboratory experiments on intact humans during exoskeleton assisted hopping. Mechanical assistance led to reduced estimated metabolic cost and MTU apparent efficiency, but increased apparent efficiency for the MTU + Exo system as a whole. Findings from this study suggest that the increased natural resonant frequency of the artificially stiffened MTU + Exo system, along with invariant movement frequencies, may underlie observed limits on the benefits of exoskeleton assistance. Our novel approach demonstrates that it is possible to capture the salient features of human locomotion with exoskeleton assistance in an isolated muscle-tendon preparation, and introduces a powerful new tool for detailed, direct examination of how assistive devices affect muscle-level neuromechanics and energetics.     

SEM observations of the elastic networks in canine femoral artery

Scanning electron microscopy was used to study the normal architectural arrangement of elastic tissue in a medium-sized muscular artery. Selective NaOH sonication digestion or formic acid digestion was used to expose and isolate the elastic networks in the femoral arteries of four healthy dogs. The digested segments were neutralized and freeze-dried before mounting for scanning electron microscopy (SEM) observation. The fenestrated internal elastic lamina (IEL) had a smooth surface with scattered regions of the fine elastic fibers that made up lacy networks protruding from the luminal surface. Prominent ellipsoid fenestrae, randomly scattered across the surface, were grouped into small and large sizes based on their mean diameter. The openings of most fenestrae were bridged by elastic fibers to give the fenestrae a sieve-like appearance. Large, transversely oriented, fusiform gaps were randomly scattered along the length of the IEL. These gaps, filled in by an elastic fiber network, sometimes spanned as much as a quarter of the vessel circumference. It is suggested that these gaps represent splits in the IEL that have been repaired. The tunica media contained a complex network of anastomosing elastic fibers and lamellae that were primarily circumferential in orientation. A well-defined external elastic lamina formed a solid sheet at the junction of the tunica media and the tunica adventitia. The tunica adventitia contained 8-10 incomplete lamellae of large, interconnecting, longitudinally oriented fibers. The architecture of the elastic network in canine femoral artery was compared with that previously described in medium-sized canine veins and in the rat femoral artery.     

Some mechanical properties of goose femoral cortical bone

The ultimate compressive strength and modulus of elasticity of femoral cortical bone from adult geese (Anser anser), were determined by sex and by quadrant by compressing small right circular cylinders which were 2.4 mm in height and 0.8 mm in diameter. The average ultimate compressive strength was 183 +/- 29 MPa. The average modulus of elasticity was 13.2 +/- 3.4 GPa. The bending strength and bending modulus of elasticity were determined by a three point bend test on rectangular prisms which had the approximate dimensions 0.75 mm X 0.75 mm X 25 mm. The average bending strength was 263 +/- 44 MPa while the average bending modulus was 19.6 +/- 3.1 GPa. The calcium content was determined by atomic absorption spectrophotometry and no correlation was found with the mechanical properties. The histology of the cortical bone was examined both quantitatively and qualitatively. A unique type of Haversian bone is described. Goose bone was found to be morphologically similar to adolescent human bone and to have mechanical properties similar to those of adult human bone.     

A new technique to measure micromotion distribution around a cementless femoral stem

The interfacial micromotion is closely associated to the long-term success of cementless hip prostheses. Various techniques have been proposed to measure them, but only a few number of points over the stem surface can be measured simultaneously. In this paper, we propose a new technique based on micro-Computer Tomography (μCT) to measure locally the relative interfacial micromotions between the metallic stem and the surrounding femoral bone. Tantalum beads were stuck at the stem surface and spread at the endosteal surface. Relative micromotions between the stem and the endosteal bone surfaces were measured at different loading amplitudes. The estimated error was 10 μm and the maximal micromotion was 60 μm, in the loading direction, at 1400 N. This pilot study provided a local measurement of the micromotions in the 3 direction and at 8 locations on the stem surface simultaneously. This technique could be easily extended to higher loads and a much larger number of points, covering the entire stem surface and providing a quasi-continuous distribution of the 3D interfacial micromotions around the stem. The new measurement method would be very useful to compare the induced micromotions of different stem designs and to optimize the primary stability of cementless total hip arthroplasty.     

A mechanical model to compute elastic modulus of tissues for harmonic motion imaging

Numerous experimental and computational methods have been developed to estimate tissue elasticity. The existing testing techniques are generally classified into in vitro, invasive in vivo and non-invasive in vivo. For each experimental method, a computational scheme is accordingly proposed to calculate mechanical properties of soft biological tissues. Harmonic motion imaging (HMI) is a new technique that performs radio frequency (RF) signal tracking to estimate the localized oscillatory motion resulting from a radiation force produced by focused ultrasound. A mechanical model and computational scheme based on the superposition principle are developed in this paper to estimate the Young's modulus of a tissue mimicking phantom and bovine liver in vitro tissue from the harmonic displacement measured by HMI. The simulation results are verified by two groups of measurement data, and good agreement is shown in each comparison. Furthermore, an inverse function is observed to correlate the elastic modulus of uniform phantoms with amplitude of displacement measured in HMI. The computational scheme is also implemented to estimate 3D elastic modulus of bovine liver in vitro.     

Strains and micromotions of press-fit femoral stem prostheses

Average femoral geometry was determined from sections of 25 human femurs. A 'stem design program' was used to determine the largest femoral stem that could be introduced into the canal. The stem was fine tuned by observations of fit in Plexiglass models of the 25 femurs. This stem was called the 'Exact-Fit'. Type 1 stem was formed by grinding the anterior and posterior faces flat. Type 2 stem was formed by additionally grinding the medial and lateral faces flat. Four fresh femurs were used for the experiments. Strain gages were located on the proximal medial area and level with the distal lateral tip. Displacement transducers were mounted proximally to measure stem-bone micromotion. Vertical and anterior-posterior forces were applied to the femoral head and normal strain data obtained. The stems were then inserted in sequence and the strains and micromotions were measured. After the uncemented stems had been tested, a smaller size of 'exact-fit' stem was cemented and the tests repeated. The strains with the uncemented stems were closer to normal than with the cemented stems. For example, compressive calcar strains averaged 56% of normal uncemented compared with 30% cemented for the different loadings. The micromotion was higher uncemented, but was still at a low level. The 'exact-fit' stem gave less resultant micromotion than the type 1 and type 2 stems. The high variation of the strain results was attributed to variations in stem-bone contact and fit. The study provided information of direct application to press-fit stems in hip replacement surgery.     

Physiologically-based testing system for the mechanical characterization of prosthetic vein valves

Due to the relatively limited amount of work done to date on developing prosthetic vein (as opposed to cardiac) valves, advances in this topic require progress in three distinct areas: 1) improved device design, 2) relevant device testing conditions, and, 3) appropriate parameters for evaluation of results. It is the purpose of this paper to address two of these issues (#2 and #3) by: 1) performing a study of normal volunteers to quantify the anatomy and hemodynamic features of healthy venous valves, 2) construction of a 2-step, in vitro testing procedure, which simulates both physiologic and postural conditions seen in the lower extremity venous system, and, 3) defining several modified and new parameters which quantify dynamic valve characteristics.     

The stability evaluation of mesenchymal stem cells differentiation toward endothelial cells by chemical and mechanical stimulation

Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent cells able to differentiate into several cell lineages. Vascular endothelial growth factor (VEGF) and the shear stress associated with blood flow are considered as the most important chemical and mechanical cues that play major roles in endothelial differentiation. However, the stability of endothelial-specific gene expression has not been completely addressed yet. ADSCs in passage 3 were cultured inside the tubular silicon tubes and then exposed to VEGF or shear stress produced in a perfusion bioreactor. To investigate the differentiation, the expression levels of Flk-1, von Willebrand factor (vWF), and vascular endothelial-cadherin (VE-cadherin) were studied using Real-Time PCR. For studying the endothelial differentiation stability, mRNA levels of the genes were evaluated in certain time intervals after completion of the tests so as to determine whether the expression level of each gene in different time points was stable and remained constant or not. Application of VEGF and shear stress caused an elevation in endothelial cells’ specific genes. Although there are some changes following the days after application of mechanical and chemical stimuli, the gene expression results depicted significantly higher gene expression between sequential chemically and mechanically incited groups. In conclusion, stress alone can be a differentiating factor, by itself. Our results verified the efficient stable differentiation ability of the chemical and mechanical factors.     

Experimental evaluation of an elastic foundation model to predict contact pressures in knee replacements

Computational wear prediction is an attractive concept for evaluating new total knee replacement designs prior to physical testing and implementation. An important hurdle to such technology is the lack of in vivo contact pressure predictions. To address this issue, this study evaluates a computationally efficient simulation approach that combines the advantages of rigid and deformable body modeling. The hybrid method uses rigid body dynamics to predict body positions and orientations and elastic foundation theory to predict contact pressures between general three-dimensional surfaces. To evaluate the method, we performed static pressure experiments with a commercial knee implant in neutral alignment using flexion angles of 0, 30, 60, and 90 degrees and loads of 750, 1500, 2250, and 3000N. Using manufacturer CAD geometry for the same implant, an elastic foundation model with linear or nonlinear polyethylene material properties was implemented within a commercial multibody dynamics software program. The model's ability to predict experimental peak and average contact pressures simultaneously was evaluated by performing dynamic simulations to find the static configuration. Both the linear and nonlinear material models predicted the average contact pressure data well, while only the linear material model could simultaneously predict the trends in the peak contact pressure data. This novel modeling approach is sufficiently fast and accurate to be used in design sensitivity and optimization studies of knee implant mechanics and ultimately wear.     

A mathematical model for the elastic and fluid mechanical behavior of the human eye

A simplified mathematical model for the eye is proposed. This idealized model simulates the aquaous flow and intraocular pressure behavior of the human eye. Starting from elementary concepts in elasticity and fluid mechanics, one can derive differential equations governing the behavior of the mathematical model. When integrated, these equations yield algebraic relationships which are closely related to some of the widely used empirical formulae in ophthalmology, e.g., Friedenwald's (1948) formula for the scleral rigidity coefficient and Grant's (1950) equation for the facility of aqueous outflow. The eye's intraocular pressure variations are simply related to its aqueous and blood volume changes if one assumes that ocular tissue has essentially linear elastic properties. St. Helen's and McEwen's (1961) experiments indicate that a linear approximation is reasonably accurate if the standard Hookian stress strain law is modified to take into account the anelastic or time-dependent elastic behavior of the corneo-scleral membrane. The last part of the paper discusses transient phenomena in an externally disturbed eye, e.g., when a tonometer is applied. One important result is a theoretical equation to describe the mean curve that one records in a tonographic tracing. This paper represents the first attempt to formulate a mathematical model relating the over-all elastic and fluid mechanical behavior of the eye. It is hoped that the model will stimulate interst and prove useful to the medical profession in motivating future experiments and in suggesting improvements for existing empirical formulae.     

A mathematical model for the elastic and fluid mechanical behavior of the human eye

A simplified mathematical model for the eye is proposed. This idealized model simulates the aquaous flow and intraocular pressure behavior of the human eye. Starting from elementary concepts in elasticity and fluid mechanics, one can derive differential equations governing the behavior of the mathematical model. When integrated, these equations yield algebraic relationships which are closely related to some of the widely used empirical formulae in ophthalmology, e.g., Friedenwald's (1948) formula for the scleral rigidity coefficient and Grant's (1950) equation for the facility of aqueous outflow. The eye's intraocular pressure variations are simply related to its aqueous and blood volume changes if one assumes that ocular tissue has essentially linear elastic properties. St. Helen's and McEwen's (1961) experiments indicate that a linear approximation is reasonably accurate if the standard Hookian stress strain law is modified to take into account the anelastic or time-dependent elastic behavior of the corneo-scleral membrane. The last part of the paper discusses transient phenomena in an externally disturbed eye, e.g., when a tonometer is applied. One important result is a theoretical equation to describe the mean curve that one records in a tonographic tracing. This paper represents the first attempt to formulate a mathematical model relating the over-all elastic and fluid mechanical behavior of the eye. It is hoped that the model will stimulate interst and prove useful to the medical profession in motivating future experiments and in suggesting improvements for existing empirical formulae.     

Experimental and computational analysis of micromotions of an uncemented femoral knee implant using elastic and plastic bone material models

It is essential to calculate micromotions at the bone-implant interface of an uncemented femoral total knee replacement (TKR) using a reliable computational model. In the current study, experimental measurements of micromotions were compared with predicted micromotions by Finite Element Analysis (FEA) using two bone material models: linear elastic and post-yield material behavior, while an actual range of interference fit was simulated. The primary aim was to investigate whether a plasticity model is essential in order to calculate realistic micromotions. Additionally, experimental bone damage at the interface was compared with the FEA simulated range.TKR surgical cuts were applied to five cadaveric femora and micro- and clinical CT- scans of these un-implanted specimens were made to extract geometrical and material properties, respectively. Micromotions at the interface were measured using digital image correlation. Cadaver-specific FEA models were created based on the experimental set-up. The average experimental micromotion of all specimens was 53.1 ± 42.3 µm (mean ± standard deviation (SD)), which was significantly higher than the micromotions predicted by both models, using either the plastic or elastic material model (26.5 ± 23.9 µm and 10.1 ± 10.1 µm, respectively; p-value < 0.001 for both material models). The difference between the two material models was also significant (p-value < 0.001). The predicted damage had a magnitude and distribution which was comparable to the experimental bone damage. We conclude that, although the plastic model could not fully predict the micro motions, it is more suitable for pre-clinical assessment of a press-fit TKR implant than using an elastic bone model.     

Anatomical evaluation of CT-MRI combined femoral model

Background

Breast density is a significant breast cancer risk factor. Currently, there is no standard method for measuring this important factor. Work presented here represents an essential component of an ongoing project that seeks to determine the appropriate method for calibrating (standardizing) mammography image data to account for the x-ray image acquisition influences. Longer term goals of this project are to make accurate breast density measurements in support of risk studies.

Methods

Logarithmic response calibration curves and effective x-ray attenuation coefficients were measured from two full field digital mammography (FFDM) systems with breast tissue equivalent phantom imaging and compared. Normalization methods were studied to assess the possibility of reducing the amount of calibration data collection. The percent glandular calibration map functional form was investigated. Spatial variations in the calibration data were used to assess the uncertainty in the calibration application by applying error propagation analyses.

Results

Logarithmic response curves are well approximated as linear. Measured effective x-ray attenuation coefficients are characteristic quantities independent of the imaging system and are in agreement with those predicted numerically. Calibration data collection can be reduced by applying a simple normalization technique. The calibration map is well approximated as linear. Intrasystem calibration variation was on the order of four percent, which was approximately half of the intersystem variation.

Conclusion

FFDM systems provide a quantitative output, and the calibration quantities presented here may be used for data acquired on similar FFDM systems.     

A new method for transduction of mesenchymal stem cells using mechanical agitation

Applications of bone marrow-derived mesenchymal stem cells in gene therapy have been hampered by the low efficiency of gene transfer to these cells. In current transduction protocols, retrovirus particles with foreign genes make only limited contact with their target cells by passive diffusion and have short life spans, thereby limiting the chances of viral infection. We theorized that mechanically agitating the virus-containing cell suspensions would increase the movement of viruses and target cells, resulting in increase of contact between them. Application of our mechanical agitation for transduction process has increased the absorption of retrovirus particles more than five times compared to the previous static method without changing cell growth rate and viability. The addition of a mechanical agitation step increased transduction efficiency to 42%, higher than that of any other previously-known static transduction protocol.     

Spatial distribution of acoustic and elastic properties of human femoral cortical bone

The purpose of this study is to quantify the spatial distribution of acoustic velocities and elastic properties (elastic constants) on Human femoral cortical bone. Four cross sections (average thickness of 2.09+/-0.27 mm) have been cut transversally between 40% and 70% of the total length and between them parallelepiped samples in each quadrant have been cut. Ultrasonic technique in transmission with immersion focused transducers at 5 MHz and contact transducers 2.25 MHz were used on the cross sections and parallelepiped samples, respectively. The first technique allows relative spatial distribution of velocities to be obtained, meanwhile the second technique allows the direct assessment of elastic constants. For both techniques, bulk velocities were found to be lower at the posterior side with an increase along the length (from 40% to 70% total length) (p < 0.05). Densities and elastic constants show equivalent pattern of variation. These variations are mainly due the cortical porosity related to vascularisation environment. The spatial distribution of velocities exhibits significant radial variation from the endosteal to the periosteal region. This is in agreement with variation of the porosity at that location. Same range of velocities was obtained with both techniques. The range of longitudinal velocities values varies from 3548 to 3967 m/s and between 18.5 and 33.1 GPa for the bulk velocities and axial elastic constants, respectively. Our results are within the range with those found in the literature. However, it must be noted that the range of acoustic and elastic properties variation is concerning the same bone. So, our new results show the ability of the technique to quantify accurately local variation of acoustic and elastic properties (within the section and along the length) of human cortical bone. Furthermore, our immersion technique could be used to assess the spatial distribution of the elastic constants with the knowledge of spatial distribution of densities.