Effect of particles with repulsive interactions enclosed in both rigid spherical shells and flexible fluid vesicles studied by Monte Carlo simulation.

Experimental observations indicate that the repulsion of particles is a factor that induces the transformation of vesicles containing multiple particles. Metropolis Monte Carlo simulations are performed with two models in which repulsive particles are enclosed inside a vesicle. The distribution of the particles and the effective bending coefficient and surface tension of the membrane are analyzed. The shape and internal structure of the vesicle containing the particles are investigated as the vesicle volume is decreased. It is revealed that the repulsive interaction between particles produces a layered structure and stiffens the membrane. When particles repulsively interact over a long range, the membrane takes on a dumbbell form.

Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation.

Peptides with cell attachment activity are beneficial component of biomaterials for tissue engineering. Conformational structure is one of the important factors for the biological activities. The EF1 peptide (DYATLQLQEGRLHFMFDLG) derived from laminin promotes cell spreading and cell attachment activity mediated by α2ß1 integrin. Although the sequence of the EF2 peptide (DFATVQLRNGFPYFSYDLG) is homologous sequence to that of EF1, EF2 does not promote cell attachment activity. To determine whether there are structural differences between EF1 and EF2, we performed replica exchange molecular dynamics (REMD) simulations and conventional molecular dynamics (MD) simulations. We found that EF1 and EF2 had ß-sheet structure as a secondary structure around the global minimum. However, EF2 had variety of structures around the global minimum compared with EF1 and has easily escaped from the bottom of free energy. The structural fluctuation of the EF1 is smaller than that of the EF2. The structural variation of EF2 is related to these differences in the structural fluctuation and the number of the hydrogen bonds (H-bonds). From the analysis of H-bonds in the ß-sheet, the number of H-bonds in EF1 is larger than that in EF2 in the time scale of the conventional MD simulation, suggesting that the formation of H-bonds is related to the differences in the structural fluctuation between EF1 and EF2. From the analysis of other non-covalent interactions in the amino acid sequences of EF1 and EF2, EF1 has three pairs of residues with hydrophobic interaction, and EF2 has two pairs. These results indicate that several non-covalent interactions are important for structural stabilization. Consequently, the structure of EF1 is stabilized by H-bonds and pairs of hydrophobic amino acids in the terminals. Hence, we propose that non-covalent interactions around N-terminal and C-terminal of the peptides are crucial for maintaining the ß-sheet structure of the peptides.

Palmitoleic acid induces the cardiac mitochondrial membrane permeability transition despite the presence of L-carnitine.

Although palmitoleic acid (C16:1) is associated with arrhythmias, and increases in an age-dependent matter, the effects of L-carnitine, which is essential for the transport of long-chain fatty acids into the mitochondria, are unclear. It has been postulated that L-carnitine may attenuate palmitate (C16:0)-induced mitochondrial dysfunction and the apoptosis of cardiomyocytes. The aim of this study was to elucidate the activity of L-carnitine in the prevention of the palmitoleic acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoleoyl-CoA-induced mitochondrial respiration was not accelerated by L-carnitine treatment, and this respiration was slightly inhibited by oligomycin, which is an inhibitor of ATP synthase. Despite pretreatment with L-carnitine, the mitochondrial membrane potential decreased and mitochondrial swelling was induced by palmitoleoyl-CoA. In the presence of a combination of L-carnitine and tiron, a free radical scavenger, there was attenuated mitochondrial swelling and cytochrome c release following palmitoleoyl-CoA treatment. We concluded that palmitoleic acid, but not palmitate, induces the cardiac mitochondrial membrane permeability transition despite the presence of L-carnitine.

Inverted micelle formation of cell-penetrating peptide studied by coarse-grained simulation: importance of attractive force between cell-penetrating peptides and lipid head group.

Arginine-rich peptide and Antennapedia are cell-penetrating peptides (CPPs) which have the ability to permeate plasma membrane. Deformation of the plasma membrane with CPPs is the key to understand permeation mechanism. We investigate the dynamics of CPP and the lipid bilayer membrane by coarse-grained simulation. We found that the peptide makes inverted micelle in the lipid bilayer membrane, when the attractive potential between the peptide and lipid heads is strong. The inverted micelle is formed to minimize potential energy of the peptide. For vesicle membrane, the peptide moves from the outer vesicle to the inner vesicle through the membrane. The translocation of the peptide suggests inverted micelle model as a possible mechanism of CPPs.

Three-dimensional gait analysis of adults with hip dysplasia after rotational acetabular osteotomy.

Dysplasia of the hip, the most common cause of secondary coxarthrosis, has a relatively high prevalence in Japan. Rotational acetabular osteotomy (RAO) is an interventional strategy that seeks to reduce the abnormal amount of high stress concentration in the acetabulum and thereby to prevent the development of coxarthrosis. Long-term clinical results have been reported, but functional evaluations of the gait before and after RAO are underreported. The aim of our recently initiated long-term prospective study is to assess the effect of RAO on the gait characteristics of patients using quantitative gait analysis. Thus far 22 patients (1 male, 21 females; mean age 30 years, range 15-43 years) have been enrolled, treated, and completed the preoperative and postoperative gait analyses. Hip pain during walking decreased in all patients after the RAO. The postoperative hip extension motion angle on the treated side increased significantly and correlated positively with the improvement in the Japanese Orthopaedic Association (JOA) pain score. The current study shows that coxalgia and gait function improved after RAO.