Normal red blood cells' shape stabilized by membrane's in-plane ordering.

Red blood cells (RBCs) are present in almost all vertebrates and their main function is to transport oxygen to the body tissues. RBCs' shape plays a significant role in their functionality. In almost all mammals in normal conditions, RBCs adopt a disk-like (discocyte) shape, which optimizes their flow properties in vessels and capillaries. Experimentally measured values of the reduced volume (v) of stable discocyte shapes range in a relatively broad window between v ~ 0.58 and 0.8. However, these observations are not supported by existing theoretical membrane-shape models, which predict that discocytic RBC shape is stable only in a very narrow interval of v values, ranging between v ~ 0.59 and 0.65. In this study, we demonstrate that this interval is broadened if a membrane's in-plane ordering is taken into account. We model RBC structures by using a hybrid Helfrich-Landau mesoscopic approach. We show that an extrinsic (deviatoric) curvature free energy term stabilizes the RBC discocyte shapes. In particular, we show on symmetry grounds that the role of extrinsic curvature is anomalously increased just below the nematic in-plane order-disorder phase transition temperature.

A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy.

It was the aim of this work to determine whether the plasma concentration of extracellular vesicles (EVs) in active diabetic Charcot neuroarthropathy (CN) is connected to the inflammatory markers, temperature elevation in the affected foot and concentration of soluble receptor for advanced glycation end products (RAGE). EVs were isolated from peripheral blood of 35 patients with active CN. EVs were counted after repetitive centrifugation and washing of samples, by flow cytometry. Foot temperature was measured by infrared thermometer. Concentration of soluble receptor for advanced glycation end products (RAGE) was determined by enzyme-linked immunosorbent assay (ELISA). We found statistically significant correlations of EV concentration (but not soluble RAGE concentration) with C-Reactive Protein (CRP) and with temperature difference between the affected and the contralateral foot (r=0.40, p=0.032; r=0.89, p<10-8, respectively). We provide evidence that the concentration of EVs is related to elevation of markers of inflammation (CRP and foot temperature difference) in acute Diabetic CN. EV-based markers could be considered as a potential aid in early diagnosis of CN.

Band edge engineering of TiO2@DNA nanohybrids and implications for capacitive energy storage devices.

Novel mesoporous TiO2@DNA nanohybrid electrodes, combining covalently encoded DNA with mesoporous TiO2 microbeads using dopamine as a linker, were prepared and characterised for application in supercapacitors. Detailed information about donor density, charge transfer resistance and chemical capacitance, which have an important role in the performance of an electrochemical device, were studied by electrochemical methods. The results indicated the improvement of electrochemical performance of the TiO2 nanohybrid electrode by DNA surface functionalisation. A supercapacitor was constructed from TiO2@DNA nanohybrids with PBS as the electrolyte. From the supercapacitor experiment, it was found that the addition of DNA played an important role in improving the specific capacitance (Cs) of the TiO2 supercapacitor. The highest Cs value of 8 F g(-1) was observed for TiO2@DNA nanohybrids. The nanohybrid electrodes were shown to be stable over long-term cycling, retaining 95% of their initial specific capacitance after 1500 cycles.

Titanium nanostructures for biomedical applications.

Titanium and titanium alloys exhibit a unique combination of strength and biocompatibility, which enables their use in medical applications and accounts for their extensive use as implant materials in the last 50 years. Currently, a large amount of research is being carried out in order to determine the optimal surface topography for use in bioapplications, and thus the emphasis is on nanotechnology for biomedical applications. It was recently shown that titanium implants with rough surface topography and free energy increase osteoblast adhesion, maturation and subsequent bone formation. Furthermore, the adhesion of different cell lines to the surface of titanium implants is influenced by the surface characteristics of titanium; namely topography, charge distribution and chemistry. The present review article focuses on the specific nanotopography of titanium, i.e. titanium dioxide (TiO2) nanotubes, using a simple electrochemical anodisation method of the metallic substrate and other processes such as the hydrothermal or sol-gel template. One key advantage of using TiO2 nanotubes in cell interactions is based on the fact that TiO2 nanotube morphology is correlated with cell adhesion, spreading, growth and differentiation of mesenchymal stem cells, which were shown to be maximally induced on smaller diameter nanotubes (15 nm), but hindered on larger diameter (100 nm) tubes, leading to cell death and apoptosis. Research has supported the significance of nanotopography (TiO2 nanotube diameter) in cell adhesion and cell growth, and suggests that the mechanics of focal adhesion formation are similar among different cell types. As such, the present review will focus on perhaps the most spectacular and surprising one-dimensional structures and their unique biomedical applications for increased osseointegration, protein interaction and antibacterial properties.

Effect of cup inclination on predicted contact stress-induced volumetric wear in total hip replacement.

In order to increase the lifetime of the total hip endoprosthesis, it is necessary to understand mechanisms leading to its failure. In this work, we address volumetric wear of the artificial cup, in particular the effect of its inclination with respect to the vertical. Volumetric wear was calculated by using mathematical models for resultant hip force, contact stress and penetration of the prosthesis head into the cup. Relevance of the dependence of volumetric wear on inclination of the cup (its abduction angle ϑA) was assessed by the results of 95 hips with implanted endoprosthesis. Geometrical parameters obtained from standard antero-posterior radiographs were taken as input data. Volumetric wear decreases with increasing cup abduction angle ϑA. The correlation within the population of 95 hips was statistically significant (P = 0.006). Large cup abduction angle minimises predicted volumetric wear but may increase the risk for dislocation of the artificial head from the cup in the one-legged stance. Cup abduction angle and direction of the resultant hip force may compensate each other to achieve optimal position of the cup with respect to wear and dislocation in the one-legged stance for a particular patient.

Spatial variation of permittivity of an electrolyte solution in contact with a charged metal surface: a mini review.

Contact between a charged metal surface and an electrolyte implies a particular ion distribution near the charged surface, i.e. the electrical double layer. In this mini review, different mean-field models of relative (effective) permittivity are described within a simple lattice model, where the orientational ordering of water dipoles in the saturation regime is taken into account. The Langevin-Poisson-Boltzmann (LPB) model of spatial variation of the relative permittivity for point-like ions is described and compared to a more general Langevin-Bikerman (LB) model of spatial variation of permittivity for finite-sized ions. The Bikerman model and the Poisson-Boltzmann model are derived as limiting cases. It is shown that near the charged surface, the relative permittivity decreases due to depletion of water molecules (volume-excluded effect) and orientational ordering of water dipoles (saturation effect). At the end, the LPB and LB models are generalised by also taking into account the cavity field.

Mechanics and electrostatics of the interactions between osteoblasts and titanium surface.

Due to oxidation and adsorption of chloride and hydroxyl anions, the surface of titanium (Ti) implants is negatively charged. A possible mechanism of the attractive interaction between the negatively charged Ti surface and the negatively charged osteoblasts is described theoretically. It is shown that adhesion of positively charged proteins with internal charge distribution may give rise to attractive interaction between the Ti surface and the osteoblast membrane. A dynamic model of the osteoblast attachment is presented in order to study the impact of geometrically structured Ti surfaces on the osteoblasts attachment. It is indicated that membrane-bound protein complexes (PCs) may increase the membrane protrusion growth between the osteoblast and the grooves on titanium (Ti) surface and thereby facilitate the adhesion of osteoblasts to the Ti surface. On the other hand, strong local adhesion due to electrostatic forces may locally trap the osteoblast membrane and hinder the further spreading of osteointegration boundary. We suggest that the synergy between these two processes is responsible for successful osteointegration along the titanium surface implant.

Attachment of rod-like (BAR) proteins and membrane shape.

Previous studies have shown that cellular function depends on rod-like membrane proteins, among them Bin/Amphiphysin/Rvs (BAR) proteins may curve the membrane leading to physiologically important membrane invaginations and membrane protrusions. The membrane shaping induced by BAR proteins has a major role in various biological processes such as cell motility and cell growth. Different models of binding of BAR domains to the lipid bilayer are described. The binding includes hydrophobic insertion loops and electrostatic interactions between basic amino acids at the concave region of the BAR domain and negatively charged lipids. To shed light on the elusive binding dynamics, a novel experiment is proposed to expand the technique of single-molecule AFM for the traction of binding energy of a single BAR domain.

Association between sub-clinical acetabular dysplasia and a younger age at hip arthroplasty in idiopathic osteoarthritis.

This retrospective study was designed to investigate whether sub-clinical acetabular dysplasia, defined by a reduced centre-edge angle of Wiberg, was associated with a younger age at hip arthroplasty in patients with idiopathic osteoarthritis (OA). Fifty-four patients with 69 performed arthroplasties and no previous referral for hip dysplasia were selected from a list of consecutive recipients of hip endoprostheses due to idiopathic OA. The centre-edge angle was measured from standard pelvic radiographs taken a mean of 5.1 years prior to the endoprosthesis operation when there were minimal signs of hip OA. The age at which hip arthroplasty was carried out was compared between those patients with low (20 degrees - 35 degrees ) and those with high (>or= 35 degrees ) centre-edge angles. The mean age at hip arthroplasty was significantly younger in the group with centre-edge angles of 20 degrees - 35 degrees (65.6 years) compared with those with centre-edge angles >or= 35 degrees (69.2 years). These results suggest that sub-clinical acetabular dysplasia was associated with a younger age at hip arthroplasty in idiopathic OA.

Kinetic and pharmacological properties of [(3)H]-histamine transport into cultured type 1 astrocytes from neonatal rats.

OBJECTIVE AND DESIGN: Astrocytes actively participate in the inactivation of neurotransmitters. In this work we elucidated the contribution of astrocytes in clearance of histamine, a process which has not yet been fully clarified. METHODS: The characteristics of [(3)H]-histamine uptake were determined in cultured neonatal rat type 1 astrocytes and histamine-N-methyl-transferase expression was determined using RT-PCR. RESULTS: These cells transport [(3)H]-histamine in a time- and concentration-dependent manner. The histamine clearance by astrocytes was described by a mathematical model including two processes: electrodiffusion and active transport. A further analysis of kinetic parameters of a carrier-operated transport revealed a single transport system with Michaelis constant (K(m)) of 3.5 +/- 0.8 microM and a maximal uptake rate (V(max)) of 7.9 +/- 0.3 pmol/mg protein/min. From drugs tested amitriptyline, desipramine, mepyramine and cimetidine significantly decreased [(3)H]-histamine uptake. Taken-up histamine could be metabolically degraded in cultured astrocytes, since they express mRNA for enzyme histamine-N-methyltransferase. CONCLUSIONS: Astrocytes participate in the clearance of extracellular histamine by electrodiffusion and active transport by a yet not identified carrier. Taken up histamine can be converted to tele-methylhistamine within astrocytes thus indicating the involvement of astrocytes not only in clearance but also in the inactivation of histamine.

The role of obesity, biomechanical constitution of the pelvis and contact joint stress in progression of hip osteoarthritis.

OBJECTIVE: The aim of our study was to explore whether earlier hip arthroplasty for idiopathic osteoarthritis (OA) might be explained by enlarged contact stress in the hip joint, and to what amount can that be attributed to obesity and biomechanical constitution of the pelvis. METHOD: Fifty subjects were selected from a list of consecutive recipients of hip endoprosthesis due to idiopathic OA; standard pelvic radiographs made years prior to surgery were the main selection criteria. For 65 hips resultant hip force and peak contact hip stress normalized to the body weight (R/Wb and p(max)/Wb) were determined from the radiographs with the HIPSTRESS method. Body weight and body mass index (BMI) were obtained with an interview. Regression analysis was used to correlate parameters of obesity (body weight, BMI), biomechanical constitution of the pelvis (R/Wb, p(max)/Wb) and mechanical loading within the hip joint (R, p(max)) with age at hip arthroplasty. RESULTS: Younger age at hip arthroplasty was associated with higher body weight (P=0.009), higher peak contact hip stress normalized to the body weight - p(max)/Wb (P=0.019), higher resultant hip force -R (P=0.027) and larger peak contact hip stress - p(max) (P<0.001), but not with BMI (P=0.121) or R/Wb (P=0.614). CONCLUSION: Our results suggest that enlarged contact stress (p(max)) plays an important role in rapid progression of hip OA with both obesity (increased body weight) and unfavorable biomechanical constitution of the pelvis (greater p(max)/Wb) contributing.

Higher peak contact hip stress predetermines the side of hip involved in idiopathic osteoarthritis.

BACKGROUND: Biomechanical parameters of the hip have been suggested to have an important influence on the development of osteoarthritis. We aimed to find out whether higher stress is generated in a hip that subsequently results in earlier hip arthroplasty compared to the contralateral hip in the same subject. METHODS: Standard anterior-posterior pelvic radiographs with no or subtle radiological signs of hip osteoarthritis, of 59 female patients, who underwent hip arthroplasty for primary osteoarthritis years later, were selected from the archives. For each subject peak contact hip stress of the hip with earlier arthroplasty and of the contralateral hip (pair of hips), was calculated from the radiographically obtained geometrical parameters with the HIPSTRESS program, which is based on a three-dimensional biomechanical model of the resultant hip force in the one-legged stance and a three-dimensional mathematical model of the contact hip stress distribution. Differences in peak contact hip stress within pairs of hips were determined for subjects with unilateral (22 pairs of hips) and bilateral disease (37 pairs of hips) by using paired-samples T-test. FINDINGS: In the population of subjects with unilateral osteoarthritis, average peak contact hip stress was significantly higher (P = 0.007) in hips with arthroplasty (2.44 kPa/N) than in contralateral hips (2.32 kPa/N). In the population of subjects with bilateral osteoarthritis, average peak contact hip stress was significantly higher (P<0.001) in hips with earlier arthroplasty (2.54 kPa/N) than in contralateral hips (2.35 kPa/N). INTERPRETATION: Results are consistent with the hypothesis that higher peak contact hip stress results in earlier hip arthroplasty due to faster development of idiopathic osteoarthritis.

High contact hip stress is related to the development of hip pathology with increasing age.

BACKGROUND: High contact hip stress is believed to be one of the key biomechanical factors involved in the hip cartilage degeneration and osteoarthritis. Accordingly, with increasing age high contact hip stress is expected to cause elimination of subjects from the population of healthy hips, but its predictive value has not been evaluated so far. The objective of the paper is to investigate whether the exposure of healthy hips to estimated high contact hip stress is related to the development of hip pathology with increasing age. METHODS: A cross-sectional age- and gender-matched analysis of the peak contact hip stress calculated from pelvic geometry was made in 103 adult subjects with healthy hips. The peak contact hip stress was calculated from anterior-posterior pelvic radiographs of healthy hips by using a mathematical model of the human hip in the static one-legged stance. FINDINGS: In both female and male population, the average values of the peak contact hip stress normalized to the body weight are significantly higher and the values are also more dispersed in younger subjects when compared to older subjects. INTERPRETATION: The hip joints which remain healthy in the old age have lower average estimated peak contact hip stress. These results are consistent with the explanation that subjects with high estimated peak contact hip stress are more likely to develop hip disease in the course of life.

Shape transformation of giant phospholipid vesicles at high concentrations of C12E8.

Giant unilamellar phospholipid vesicles were prepared by the method of electroformation from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC). We studied the influence of different concentrations of the surfactant octaethyleneglycol dodecylether (C(12)E(8)) on the spontaneous shape transformations of POPC vesicles at room temperature. In accordance with previous results, we observed that low concentration of C(12)E(8) increased the speed of the characteristic vesicle shape transformation, starting from the initial shape with thin tubular protrusion, through beaded protrusion where the number of beads gradually decreased, to final spherical shapes with invagination, whereby the average mean curvature of the vesicle membrane monotonously decreased. In contrast, higher concentration of C(12)E(8) initially induced the shape transformation in the "opposite direction": in the protrusion, the number of beads gradually increased and eventually a tube was formed whereby the average mean curvature of the vesicle membrane gradually increased. However, at a certain point, an abrupt shape change took place to yield the vesicle with invagination. In this transition, the average mean curvature of the vesicle membrane discontinuously decreased. After this transition, the vesicle began to shrink and finally disappeared. We discuss possible mechanisms involved in the observed transformations.

Polyethylene wear in total hip prostheses: the influence of direction of linear wear on volumetric wear determined from radiographic data.

PURPOSE: To develop a new mathematical model for calculating the volumetric wear of polyethylene cups from known values of the radius of the prosthesis head, the extent of linear wear and the direction of linear wear determined from standard antero-posterior radiographs. METHOD: A new mathematical model was developed. The results of this new mathematical model were compared with the results obtained using the standard, frequently used mathematical model, which takes into consideration only the radius of the prosthesis head and the extent of linear wear of the polyethylene cups. The results of both mathematical models were further compared with the results obtained by direct measurement of volumetric wear using the fluid displacement method. RESULTS: Comparison of the mathematical models shows that the average volumetric wear calculated using the new mathematical model is 8.5% smaller than the average volumetric wear determined by the fluid displacement method, while the average volumetric wear calculated by standard mathematical model is 17.5% higher. The results of the new mathematical model are, thus, notably less biased than those of the standard one. CONCLUSION: In calculating the volumetric wear from antero-posterior radiographs, not only the radius of the prosthesis head and the extent of the linear wear but also the direction of the latter has to be considered.

Influence of contact hip stress on the outcome of surgical treatment of hips affected by avascular necrosis.

INTRODUCTION: Biomechanical analysis is an important tool that could improve the treatment of a diseased hip. However, it is still unclear how the biomechanical status affects the clinical outcome of a certain disease. In this work we studied the long-term effect of contact hip stress on the clinical outcome of hips that were operated on by various intertrochanteric osteotomies due to avascular necrosis of the femoral head. The hypothesis being tested is that the hips with a more favourable postoperative distribution of contact hip stress have a better clinical outcome. MATERIALS AND METHODS: The study was performed on a population of 30 hips. For each hip, we determined the peak contact hip stress before the operation and immediately after the operation by using a recently developed method based on a three-dimensional mathematical model and the data from standard anteroposterior roentgenographs of both hips and pelvis. The hips were evaluated clinically 9-26 years after the operation and divided into a successful and an unsuccessful group. The average change of the peak stress due to the operation was calculated for each group, and the values were compared by t-test. RESULTS: In the successful group the operation caused an average decrease of the peak hip stress of about 10%, while in the unsuccessful group the operation caused an average increase of the peak hip stress of about 4%, the difference between the respective changes of the peak stress due to the operation being statistically significant ( p=0.001). CONCLUSION: Our results support the hypothesis that the hips with a more favourable postoperative distribution of contact hip stress have a better clinical outcome.

Mathematical estimation of stress distribution in normal and dysplastic human hips.

By using a mathematical model of the adult human hip in the static one-legged stance position of the body, the forces acting on the hip, peak stress in the hip joint and other relevant radiographic and biomechanical parameters were assessed. The aims were to examine if the peak stress in dysplastic hips is higher than in normal hips and to find out which biomechanical parameters contribute significantly to higher peak stress. The average normalized peak stress in dysplastic hips (7.1 kPa/N) was markedly higher (to approximately 100%) than the average normalized peak stress in normal hips (3.5 kPa/N). The characteristic parameters that contributed to higher peak stress in dysplastic hips included the smaller lateral coverage of the femoral head, the larger interhip distance, the wider pelvis, and the medial position of the greater trochanter. These results are consistent with the hypothesis that stress distribution over weight-bearing surface of the hip joint is the relevant parameter for assessment of the risk for developing coxarthrosis.

Hip stress reduction after Chiari osteotomy.

A mathematical model was developed to study the effect of the Chiari osteotomy on the distribution of contact hip stress over the weight-bearing area. It was shown that Chiari osteotomy can increase the weight-bearing area directly (on the lateral side), owing to the additional area formed by the ala ossis ilii segment, and indirectly (on the medial side), owing to the shift of the stress pole in the medial direction. As a consequence, the contact hip stress is reduced after Chiari osteotomy. The indirect effect is important and often larger than the direct one. Using the proposed mathematical model and standard anteroposterior roentgenographs from archives, the average peak stress on the weight-bearing area, normalised with respect to the body weight (pmax/ W(B)), was determined before and after Chiari osteotomy (8,310m(-2) and 4,480 m(-2), respectively) on a population of 29 dysplastic hips. The difference was statistically significant (p < 0.005). Based on the results presented, it can be concluded that the hip joint contact stress in dysplastic hips considerably decreases after Chiari osteotomy, indicating a favourable biomechanical effect of this operation.

Computer determination of contact stress distribution and size of weight bearing area in the human hip joint.

The mathematical models and the corresponding computer program for determination of the hip joint contact force, the contact stress distribution, and the size of the weight bearing area from a standard anteroposterior radiograph are described. The described method can be applied in clinical practice to predict an optimal stress distribution after different operative interventions in the hip joint and to analyze the short and long term outcome of the treatment of various pathological conditions in the hip. A group of dysplastic hips and a group of normal hips were examined, with respect to the peak contact stress normalized by the body weight, and with respect to the functional angle of the weight bearing area. It is shown that both these parameters can be used in the assessment of hip dysplasia.

Biomechanical evaluation of hip joint after Salter innominate osteotomy: a long-term follow-up study.

The biomechanical state of the hip after a Salter innominate osteotomy was investigated by using the radiographic data of 38 operated and 21 contralateral nonoperated hips from our archives. The centre-edge angle of Wiberg was determined from the radiographs taken shortly after the operation. From the radiographs of the latest follow-up (7-13 years after the operation), we also determined the peak value of contact hip joint stress normalized by the body weight, and the functional angle of the weight-bearing area. A mathematical model was used. We show that the geometrical parameters aside from the centre-edge angle may considerably influence the contact hip stress distribution. We also show that the functional angle of the weight-bearing area is a more relevant parameter than the normalized peak stress if the exact magnification of the images is not known and if there is considerable variation of the image size within the sample. The development of the centre-edge angle of the operated hips and of the contralateral hips was also studied. We found that the centre-edge angle increases on average during the follow-up time in the operated hips as well as in the contralateral nonoperated hips, but the average increase is smaller in the former. It is shown that an unfavorable stress distribution is connected to the decrease of the centre-edge angle over time. Finally, we found a weak positive correlation between the centre-edge angle shortly after the operation and the functional angle of the weight-bearing area at the of the latest follow-up.