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1	Simulations of Skin Barrier Function: Free Energies of Hydrophobic and Hydrophilic Transmembrane Pores in Ceramide Bilayers Anwar, Jamshed, Notman, R., Noro, M.G., den Otter, W.K., Briels, W.J. January 2008 (has links) No / Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel phase and in the DMSO-induced fluidized state. Our simulations show that the fluid phase bilayers form archetypal water-filled hydrophilic pores similar to those observed in phospholipid bilayers. In contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the relatively small pore diameters studied here, the hydrophobic pores are empty rather than filled with bulk water, suggesting that they do not compromise the barrier function of ceramide membranes. A phenomenological analysis suggests that these vapor pores are stable, below a critical radius, because the penalty of creating water-vapor and tail-vapor interfaces is lower than that of directly exposing the strongly hydrophobic tails to water. The PMCF free energy profile of the vapor pore supports this analysis. The simulations indicate that high DMSO concentrations drastically impair the barrier function of the skin by strongly reducing the free energy required for pore opening. / EPSRC Skin Barrier Function Membrane Pore Formation Dimethyl Sulfoxide DMSO Ceramide Bilayers Molecular Dynamics Simulations Free Energies
2	Rational design of DNA-based lipid membrane pores Göpfrich, Kerstin January 2017 (has links) DNA nanotechnology has revolutionised our capability to shape and control three-dimensional structures at sub-nanometre length scales. In this thesis, we use DNA to build synthetic membrane-inserting channels. Porphyrin and cholesterol tags serve as membrane anchors to facilitate insertion into the lipid membrane. With atomic force microscopy, confocal imaging and ionic current recordings we characterise our DNA nanochannels that mimic their natural protein-based counterparts in form and function. We find that they exhibit voltage-dependent conductance states. Amongst other architectures, we create the largest man-made pore in a lipid membrane to date approaching the electrical diameter of the nuclear pore complex. Pushing the boundaries on the other end of the spectrum, we demonstrate the ultimately smallest DNA membrane pore made from a single membrane-spanning DNA duplex. Thereby, we proof that ion conduction across lipid membranes does not always require a physical channel. With experiments and MD simulations we show that ions flow through a toroidal pore emerging at the DNA-lipid interface around the duplex. Our DNA pores spanning two orders of magnitude in conductance and molecular weight showcase the rational design of synthetic channels inspired by the diversity of nature - from ion channels to porins.
3	Caractérisation biochimique, structurale et inhibition du système de sécrétion de type IV par l’étude des protéines VirB8 Casu, Bastien 03 1900 (has links) No description available. plasmide conjugaison système de sécrétion de type IV interaction protéine- protéine criblage à base de fragments conception de médicaments résistance aux antimicrobiens protéine de type VirB8 protéine de type VirB6 pore membranaire plasmid conjugation type IV secretion system protein-protein interaction fragment-based screening drug design antimicrobial resistance VirB8-like VirB6-like membrane pore

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