Hydrophobic Mismatch Controls the Mode of Membrane-Mediated Interactions of Transmembrane Peptides

Various cellular processes require the concerted cooperative action of proteins. The possibility for such synchronization implies the occurrence of specific long-range interactions between the involved protein participants. Bilayer lipid membranes can mediate protein–protein interactions via relatively long-range elastic deformations induced by the incorporated proteins. We considered the interactions between transmembrane peptides mediated by elastic deformations using the framework of the theory of elasticity of lipid membranes. An effective peptide shape was assumed to be cylindrical, hourglass-like, or barrel-like. The interaction potentials were obtained for membranes of different thicknesses and elastic rigidities. Cylindrically shaped peptides manifest almost neutral average interactions—they attract each other at short distances and repel at large ones, independently of membrane thickness or rigidity. The hourglass-like peptides repel each other in thin bilayers and strongly attract each other in thicker bilayers. On the contrary, the barrel-like peptides repel each other in thick bilayers and attract each other in thinner membranes. These results potentially provide possible mechanisms of control for the mode of protein–protein interactions in membrane domains with different bilayer thicknesses.

A comparative study of human glomerular basement membrane thickness using direct measurement and orthogonal intercept methods

Introduction Here we report estimates of glomerular basement membrane (GBM) thickness in the Brazilian population performed using direct (DM) and orthogonal interception methods (OIM), and comment on potential sources of variation among estimates made by different laboratories. Methodology A total of 38 patients, ranging from 3 to 78 years of age, 26 (68%) males and 12 (32%) females, were submitted to kidney biopsy procedures for renal disease diagnosis. Glomeruli were diagnosed with minor histological changes by conventional, immunofluorescence and electron microscopy. GBM thickness was estimated using both DM and OIM methods. Results Estimates of GBM thickness obtained using DM were higher than those obtained by OIM. However, the application of a correction for non-perpendicular membrane sectioning to DM estimates yielded similar results to those obtained under OIM. The estimated GMB thickness using DM after correction was 289 + 44 nm, versus 287 + 48 nm by OIM. No statistically significant differences were detected in GMB thickness, nor with respect to patient age or sex. Conclusions GBM thickness in the studied Brazilian population measured approximately 290 nm. The application of criteria for estimating the shortest distance between the endothelial and podocyte cell membranes with correction for non-perpendicular membrane sectioning can increase the accuracy of GBM thickness estimates using DM and OIM.

A Novel Generation of Polysulfone/Crown Ether-Functionalized Reduced Graphene Oxide Membranes with Potential Applications in Hemodialysis

Heavy metal poisoning is a rare health condition caused by the accumulation of toxic metal ions in the soft tissues of the human body that can be life threatening if left untreated. In the case of severe intoxications, hemodialysis is the most effective method for a rapid clearance of the metal ions from the bloodstream, therefore, the development of hemodialysis membranes with superior metal ions retention ability is of great research interest. In the present study, synthetic polysulfone membranes were modified with reduced graphene oxide functionalized with crown ether, an organic compound with high metal ions complexation capacity. The physico-chemical characteristics of the composite membranes were determined by FT-IR, Raman, XPS and SEM analysis while their efficiency in retaining metal ions was evaluated via ICP-MS analysis. The obtained results showed that the thermal stability of reduced graphene oxide was improved after functionalization with crown ether and that the presence of the carbonaceous filler influenced the membranes morphology in terms of pore dimensions and membrane thickness. Moreover, the ability of Cu2+ ions retention from synthetic feed solution was up to three times higher in the case of the composite membranes compared to the neat ones.

Phase transitions of liposomes: When light meets heat

Phase transitions of liposomes are normally studied by differential scanning calorimetry (DSC). A suspension of liposomes is subjected to an increase (decrease) of temperature and when heat is absorbed (released), the liposomes transit from a gel (liquid) to a liquid (gel) phase. This endothermic (exothermic) process takes place at a temperature called the melting temperature Tm, which is distinctive of the type of lipids forming the vesicles. The vesicles, though, also modify their size in the transition. Indeed, the thickness of the membranes decreases (increases) because carbon tails misalign (align). Concomitant with the modifications in the membrane thickness, the diameter (D) of the liposomes changes too. Therefore, when they are inspected by light, the scattered signal carries information from such dilatation (contraction) process. We performed careful experiments using dynamic light scattering (DLS) as a function of temperature to detect the size changes of different liposomes. Gaussian fits of the derivatives of the D vs T curves coincide within 1% with thermograms, which hints to the possibility of performing thermodynamic studies of lipid systems employing light.

Renoprotective Effects of Metformin and Its Relationship with Oxidative Stress in Type 2 Diabetic Mice

Background: Oxidative stress has previously been shown to play critical roles in the development of diabetes and its complications. The purpose of this research was to observe the reno-protective effect of metformin and its effect on oxidative stress in type 2 diabetic mice renal tissue.Methods: Type 2 diabetes mellitus mice model was established by High-fat feed combined with small-dose STZ and randomly divided into diabetes model group, Metformin [MET, 250mg/(kg.d)] group, Glibenclamide (GLIB) [GLIB, 2.5mg/(kg.d)] group, and normal control group (NC). After 8 weeks of intervention, blood and urine samples were collected for detection of FBG, HbA1c, urine albumin (Alb), retinol-binding protein (RBP), podocalyxin (PCX), 8-OHdG, 8-iso-PG, and creatinine (Cr). Renal tissue specimens were preserved for observing renal glomerular basement membrane thickness (GBMT) and foot process fusion rate (FPFR) under electron microscopy.Results: Compared with the NC group, FBG, HbA1c, urinary Alb/Cr (UACR), RBP/Cr (URCR), PCX/Cr (UPCR), 8-OHdG /Cr (UOHCR), and 8-iso-PG /Cr (UISOCR) significantly increased in the T2DM group (P <0.05). Compared with the T2DM group, FBG, HbA1c, UACR, URCR, UPCR, UOHCR, and UISOCR were significantly reduced in the GLIB group and MET group (P <0.05). Compared to the GLIB group, UACR, URCR, UPCR, UOHCR, and UISOCR decreased in the MET group (P <0.05), but FBG and HbA1c were not differenced statistically between the two groups. GBMT and FPFR increased in the T2DM group (P <0.05), which were reduced in the MET group and lighter than those in the GLIB group (P <0.05).Conclusion: Metformin intervention can play a reno-protective effect in type 2 diabetic mice, which may be related to its effect in inhibiting enhanced oxidative stress in vivo.

Numerical Simulation on Impacts of Thickness of Nafion Series Membranes and Relative Humidity on PEMFC Operated at 363 K and 373 K

The purpose of this study is to understand the impact of the thickness of Nafion membrane, which is a typical polymer electrolyte membrane (PEM) in Polymer Electrolyte Membrane Fuel Cells (PEMFCs), and relative humidity of supply gas on the distributions of H2, O2, H2O concentration and current density on the interface between a Nafion membrane and anode catalyst layer or the interface between a Nafion membrane and cathode catalyst layer. The effect of the initial temperature of the cell (Tini) is also investigated by the numerical simulation using the 3D model by COMSOL Multiphysics. As a result, the current density decreases along with the gas flow through the gas channel irrespective of the Nafion membrane thickness and Tini, which can be explained by the concentration distribution of H2 and O2 consumed by electrochemical reaction. The molar concentration of H2O decreases when the thickness of Nafion membrane increases, irrespective of Tini and the relative humidity of the supply gas. The current density increases with the increase in relative humidity of the supply gas, irrespective of the Nafion membrane thickness and Tini. This study recommends that a thinner Nafion membrane with well-humidified supply gas would promote high power generation at the target temperature of 363 K and 373 K.

Optimization of an in silico protocol to characterize membrane PAINS

Membrane Pan-Assay INterference compoundS (PAINS) are a class of molecules that interact non-specifically with lipid bilayers and alter their physicochemical properties. An early identification of these compounds avoids chasing false leads and the needless waste of time and resources in drug discovery campaigns. In this work, we optimized an in silico protocol based on umbrella sampling (US)/MD simulations to discriminate between compounds with different membrane PAINS behavior. We showed that the method is quite sensitive to membrane thickness fluctuations, which was mitigated by changing the US-reference position to the P-atoms of the closest interacting monolayer. The computational efficiency was improved further by decreasing the number of umbrellas and adjusting their strength and position in our US scheme. The ISDM-calculated membrane permeability coefficients confirmed that resveratrol and curcumin have distinct membrane PAINS characteristics and indicate a misclassification of nothofagin in a previous work. Overall, we have presented here a promising in silico protocol which can be adopted as a future reference method to identify membrane PAINS.

Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection

Ungual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes, healthy or infected with Trichophyton rubrum, underwent different imaging techniques highlighting that continuous pores traversed the entire membrane and infection resulted in fungal growth, both superficial, as well as in the membrane’s matrix. These membrane characteristics resulted in substantial differences in the permeation of the antifungal model substance bifonazole, depending on the dosage forms. Increasing the thickness of healthy membranes from 100 µm to 400 µm disproportionally reduced the permeated amount of bifonazole from the liquid and semisolid forms and allowed for a more pronounced assessment of the effects by excipients, such as urea as the permeation enhancer. Similarly, an infection of 400-µm membranes drastically increased the permeated amount. Therefore, the thickness and infection statuses of the membranes in the permeation experiments were essential for a differential readout, and standardized formulation-dependent experimental setups would be highly beneficial.

High-frequency oscillations of low-voltage dielectric elastomer actuators

To increase safety and reduce the electric circuit cost, Dielectric elastomer actuators (DEAs) must operate below the kV range. The simplest strategy to reduce the voltage operation is to decrease the dielectric elastomer membrane thickness. This research aims to demonstrate DEAs with a nanometric uniform thickness that can operate at a low voltage (below 70 V) and a high frequency. We use the roll-to-roll process to fabricate a 600-nm-thick stretchable PDMS (polydimethylsiloxane) nanosheet and a 200-nm-thick conductive nanosheet. These nanosheet-DEAs are tested in high-frequency operations of DC voltage below 70 V and in a frequency range of 1–30 kHz.