A unified model for the biogenesis of mitochondrial outer membrane multi-span proteins

The mitochondrial outer membrane (MOM) harbors proteins that traverse the membrane via several helical segments, so-called multi-span proteins. Two contradicting mechanisms were suggested to describe their integration into the MOM. The first proposes that the mitochondrial import (MIM) complex facilitates this process and functions as an insertase, whereas the second suggests that such proteins can integrate into the lipid phase without the assistance of import factors in a process that is enhanced by phosphatidic acid. To resolve this discrepancy and obtain new insights on the biogenesis of these proteins, we addressed this issue using yeast mitochondria and the multi-span protein Om14. Testing different truncation variants, we show that only the full-length protein contains all the required information that assure targeting specificity. Employing a specific insertion assay and several single and double deletion strains, we show that neither the import receptor Tom70 nor any other protein with a cytosolically exposed domain have a crucial contribution to the biogenesis process. We further demonstrate that Mim1 and Porin are required for optimal membrane integration of Om14 but none of them is absolutely required. Unfolding of the newly synthesized protein, its optimal hydrophobicity, as well as higher fluidity of the membrane dramatically enhanced the import capacity of Om14. Collectively, our findings suggest that MOM multi-span proteins can follow different biogenesis pathways in which proteinaceous elements and membrane behavior contribute to a variable extent to the combined efficiency.

Lipid Interactions Between Flaviviruses and Mosquito Vectors

Mosquito-borne flaviviruses, such as dengue (DENV), Zika (ZIKV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses, threaten a large part of the human populations. In absence of therapeutics and effective vaccines against each flaviviruses, targeting viral metabolic requirements in mosquitoes may hold the key to new intervention strategies. Development of metabolomics in the last decade opened a new field of research: mosquito metabolomics. It is now clear that flaviviruses rely on mosquito lipids, especially phospholipids, for their cellular cycle and propagation. Here, we review the biosyntheses of, biochemical properties of and flaviviral interactions with mosquito phospholipids. Phospholipids are structural lipids with a polar headgroup and apolar acyl chains, enabling the formation of lipid bilayer that form plasma- and endomembranes. Phospholipids are mostly synthesized through the de novo pathway and remodeling cycle. Variations in headgroup and acyl chains influence phospholipid physicochemical properties and consequently the membrane behavior. Flaviviruses interact with cellular membranes at every step of their cellular cycle. Recent evidence demonstrates that flaviviruses reconfigure the phospholipidome in mosquitoes by regulating phospholipid syntheses to increase virus multiplication. Identifying the phospholipids involved and understanding how flaviviruses regulate these in mosquitoes is required to design new interventions.

Membrane Action of Cladding Subjected to Blast Loading and Effects on the Supporting Structure

A recent blast design trend is to properly select cladding characteristics in order to limit blast consequences on its supporting structure. In this context, it is worth noting that cladding components may exhibit significant membrane action, and its effects may be decisive for the supporting structure. The main focus of the present study was to examine these effects through two-step dimensionless SDOF analyses, aimed at reaching conclusions that would be applicable to a large variety of cladding/supporting structure arrangements. The results of these analyses are presented by employing the dynamic load factor, representing the maximum supporting structure displacement. It was found that cladding membrane action has adverse effects over its supporting structure, as it does not allow for extensive plastic dissipation and leads to higher support reactions. On the contrary, insignificant membrane action leads to lower dynamic load factor for the supporting structure. Thus, membrane behavior should be activated only as a safety backup action in order to prevent cladding failure. A case study of a typical cladding/supporting structure is presented to demonstrate and verify the proposed two-step SDOF analyses and the obtained results.

CD82 and Gangliosides Tune CD81 Membrane Behavior

Tetraspanins are a family of transmembrane proteins that form a network of protein–protein interactions within the plasma membrane. Within this network, tetraspanin are thought to control the lateral segregation of their partners at the plasma membrane through mechanisms involving specific lipids. Here, we used a single molecule tracking approach to study the membrane behavior of tetraspanins in mammary epithelial cells and demonstrate that despite a common overall behavior, each tetraspanin (CD9, CD81 and CD82) has a specific signature in terms of dynamics. Furthermore, we demonstrated that tetraspanin dynamics on the cell surface are dependent on gangliosides. More specifically, we found that CD82 expression increases the dynamics of CD81 and alters its localization at the plasma membrane, this has no effect on the behavior of CD9. Our results provide new information on the ability of CD82 and gangliosides to differentially modulate the dynamics and organization of tetraspanins at the plasma membrane and highlight that its lipid and protein composition is involved in the dynamical architecture of the tetraspanin web. We predict that CD82 may act as a regulator of the lateral segregation of specific tetraspanins at the plasma membrane while gangliosides could play a crucial role in establishing tetraspanin-enriched areas.

Fluid-Structure Interaction Analysis on Membrane Behavior of a Microfluidic Passive Valve

In this paper, the effect of membrane features on flow characteristics in the microfluidic passive valve (MPV) and the membrane behavior against fluid flow are studied using the fluid-structure interaction (FSI) analysis. Firstly, the microvalve model with different numbers of microholes and pitches of microholes are designed to investigate the flow rate of the MPV. The result shows that the number of microholes on the membrane has a significant impact on the flow rate of the MPV, while the pitch of microholes has little effect on it. The constant flow rate maintained by the microvalve (the number of microholes n = 4) is 5.75 mL/min, and the threshold pressure to achieve the flow rate is 4 kPa. Secondly, the behavior of the membrane against the fluid flow is analyzed. The result shows that as the inlet pressure increases, the flow resistance of the MPV increases rapidly, and the deformation of the membrane gradually becomes stable. Finally, the effect of the membrane material on the flow rate and the deformation of the membrane are studied. The result shows that changes in the material properties of the membrane cause a decrease in the amount of deformation in all stages the all positions of the membrane. This work may provide valuable guidance for the optimization of microfluidic passive valve in microfluidic system.