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Defense of the thesis of Mariia Savenko

Mariia Savenko->] is pleased to invite you to her thesis defense entitled: Numerical studies of supported or bacterial lipid membranes.
The defense will take place on Friday September 29 at 2:30 pm in amphitheater B (metrology building).

Invitation to download ICI

Jury composition
- Ms Baud Stéphanie, Professor, University of Reims Champagne-Ardenne, Rapporteur
- Mr D’Amelio Nicola, Professor Université de Picardie Jules Verne, Rapporteur
- Ms Duboué-Dijon Élise, Chargée de recherche Université Paris Cité, Jury member
- Mr Trouillas Patrick, Professor, University of Limoges, Jury member
- Mr. Ramseyer Christophe, Professor Université de Franche-Comté, Thesis Director

The use of molecules targeting the lipid matrix of bacterial membranes is one of the avenues currently being explored to tackle growing antibiotic resistance. Gram-negative bacteria are an important target, as the presence of an outer membrane (OM) reduces effective antibiotic classes and confers specific resistance mechanisms directly linked to the presence of lipopolysaccharides. In this work, we modeled OM and various phospholipid membranes to address two complementary issues. On the one hand, a wide range of experiments designed to study the action of drugs on membranes require their immobilization, which is often achieved by deposition on hydrophilic substrates. However, substrate-membrane interactions can alter the biological functions and structural properties of membranes. We therefore applied molecular dynamics simulations to predict changes in lipid membrane structure as a function of substrate properties. In particular, we have shown that the structure of deposited lipid systems varies gradually between that of a self-assembled monolayer (SAM) and that of a supported lipid bilayer (SLB), depending on the hydrophilicity of the substrate. Subsequently, we designed a collective variable that describes the adsorption process, in order to estimate the free energy profile. This method can be used to predict the energetically favorable states of supported lipid bilayers for a given surface. On the other hand, we focused on the mode of action of colistin, a polymyxin lipopeptide currently used as a last resort, partly because of its high toxicity, but also to stem the emergence of resistant strains. Polymyxins are known to target OM, potentially by displacing the divalent ions that contribute to its stability. We designed a new collective variable to understand how local inhomogeneities in divalent ion density affect OM. We modeled the OM using both coarse-grained and all-atom force fields. Using coarse-grained simulations, we observed that membrane fluidity is strongly affected by the creation of this inhomogeneity, and that colistin further promotes these changes in LPS mobility.

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