A method to determine whether a musculoskeletal model can resist arbitrary external loadings within a prescribed range

Computational models of the musculoskeletal system are prone to design errors. It is possible to create a model that cannot satisfy equilibrium conditions for a set of external loading conditions. A model is ‘loadable’ if there exists a set of muscle forces that can resist an arbitrary applied force within a prescribed range. In this study, a novel mathematical method is introduced to determine whether models are loadable. In addition, an idealised musculoskeletal model is presented in order to develop the theory behind the mathematical method. The method uses the simplex algorithm to determine feasibility of the linear programming problem and can determine loadability for an arbitrary, continuous range of external forces. The method was applied to a three-dimensional model of the shoulder and correctly determined loadability for a range of externally applied forces.     

Development of software for human muscle force estimation

Muscle force estimation (MFE) has become more and more important in exploring principles of pathological movement, studying functions of artificial muscles, making surgery plan for artificial joint replacement, improving the biomechanical effects of treatments and so on. At present, existing software are complex for professionals, so we have developed a new software named as concise MFE (CMFE). CMFE which provides us a platform to analyse muscle force in various actions includes two MFE methods (static optimisation method and electromyographic-based method). Common features between these two methods have been found and used to improve CMFE. A case studying the major muscles of lower limb of a healthy subject walking at normal speed has been presented. The results are well explained from the effect of the motion produced by muscles during movement. The development of this software can improve the accuracy of the motion simulations and can provide a more extensive and deeper insight in to muscle study.     

Surface EMG-force modelling for the biceps brachii and its experimental evaluation during isometric isotonic contractions

The aim of this study was to evaluate a surface electromyography (sEMG) signal and force model for the biceps brachii muscle during isotonic isometric contractions for an experimental set-up as well as for a simulation. The proposed model includes a new rate coding scheme and a new analytical formulation of the muscle force generation. The proposed rate coding scheme supposes varying minimum and peak firing frequencies according to motor unit (MU) type (I or II). Practically, the proposed analytical mechanogram allows us to tune the force contribution of each active MU according to its type and instantaneous firing rate. A subsequent sensitivity analysis using a Monte Carlo simulation allows deducing optimised input parameter ranges that guarantee a realistic behaviour of the proposed model according to two existing criteria and an additional one. In fact, this proposed new criterion evaluates the force generation efficiency according to neural intent. Experiments and simulations, at varying force levels and using the optimised parameter ranges, were performed to evaluate the proposed model. As a result, our study showed that the proposed sEMG–force modelling can emulate the biceps brachii behaviour during isotonic isometric contractions.     

Analysis of tendinous actuation in balancing the maximal fingertip force for normal and abnormal forefinger system

This work displayed the force capabilities of the musculoskeletal system of the forefinger under external loading. Different states of normal and pathological fingers are studied. We evaluated the impact of losing musculo-tendon unit strength capacities in terms of maximal output fingertip force and tendon tensions distribution. A biomechanical model for a static force analysis is developed through anatomical and kinematic studies. An optimisation approach is then used to determine tendon tension distribution when performing an isometric task. Furthermore, pathological fingers with common cases of injured flexors and extensors are analysed. The method of simulation for forefinger abnormities is described. Furthermore, the simulation results are interpreted.     

Validation of the Boussinesq equation for use in traction field determination

Cell traction force plays an important role in many biological processes. Several traction force microscopy methods have been developed to determine cell traction forces based on the Boussinesq solution. This approach, however, is rooted in a half-space assumption. The purpose of this study was to determine the error induced in the half-space assumption using a finite element method (FEM). It demonstrates that displacement error between the FEM and the Boussinesq equation can be used to measure the accuracy of the Boussinesq equation, although singularity exists in the loading point. For one concentrated force, significant difference between the FEM and the Boussinesq equation occurs in the whole field; this difference decreases with an increase in the plate thickness. However, in the case of the balanced forces, the offset of the balanced forces decreases the errors in the middle area. Overall, this study demonstrates that increasing the thickness of the polyacrylamide gel is important for reducing the error of the Boussinesq equation when determining the displacement field of the gel under loads.     

The biomechanical effect of the collar of a femoral stem on total hip arthroplasty

To investigate the biomechanical effect of collars, finite element analyses are carried out through two hip joints that are implanted using collared and collarless stems, respectively, and an intact hip joint model. For the analyses, the sacrum, coxal bone, and the cancellous and cortical bones of a femur are modelled using finite elements based on X-ray computed tomographic images taken from a 27-year-old woman. From the results, it is found that a collar with perfect calcar contact prevents stem subsidence and decreases the proximal–lateral gap and the lateral stem tilting. Therefore, it can impart reasonable biomechanical stability for total hip arthroplasty. However, its low load transmission ability and increased stem tilting effect due to the imperfect contact between the collar and the calcar are found to be serious problems that need to be solved. Results of clinical follow-up are presented for supporting the computational results.     

Rab-dependent cellular trafficking and amyotrophic lateral sclerosis

Rab GTPases are becoming increasingly implicated in neurodegenerative disorders, although their role in amyotrophic lateral sclerosis (ALS) has been somewhat overlooked. However, dysfunction of intracellular transport is gaining increasing attention as a pathogenic mechanism in ALS. Many previous studies have focused axonal trafficking, and the extreme length of axons in motor neurons may contribute to their unique susceptibility in this disorder. In contrast, the role of transport defects within the cell body has been relatively neglected. Similarly, whilst Rab GTPases control all intracellular membrane trafficking events, their role in ALS is poorly understood. Emerging evidence now highlights this family of proteins in ALS, particularly the discovery that C9orf72 functions in intra transport in conjunction with several Rab GTPases. Here, we summarize recent updates on cellular transport defects in ALS, with a focus on Rab GTPases and how their dysfunction may specifically target neurons and contribute to pathophysiology. We discuss the molecular mechanisms associated with dysfunction of Rab proteins in ALS. Finally, we also discuss dysfunction in other modes of transport recently implicated in ALS, including nucleocytoplasmic transport and the ER-mitochondrial contact regions (MAM compartment), and speculate whether these may also involve Rab GTPases.     

ANALYSIS OF LIGAND–RECEPTOR INTERACTIONS IN CELLS BY ATOMIC FORCE MICROSCOPY

ABSTRACT

Atomic force microscopy (AFM) increasingly has been used to analyse “receptor” function, either by using purified proteins (“molecular recognition microscopy”) or, more recently, in situ in living cells. The latter approach has been enabled by the use of a modified commercial AFM, linked to a confocal microscope, which has allowed adhesion forces between ligands and receptors in cells to be measured and mapped, and downstream cellular responses analysed. We review the application of AFM to cell biology and, in particular, to the study of ligand–receptor interactions and draw examples from our own work and that of others to show the utility of AFM, including for the exploration of cell surface functionalities. We also identify shortcomings of AFM in comparison to “standard” methods, such as receptor auto-radiography or immuno-detection, that are widely applied in cell biology and pharmacological analysis.