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International audience; Phase separation in hybrid polymer/lipid giant unillamelar vesicles (GHUVs) has been described over the last few years. However there is still a lack of understanding in physical and molecular factors governing the phase separation in such systems. Among these parameters it has been suggested that in analogy to multicomponent lipid vesicles that hydrophobic mismatchs as well as lipid fludity play a role.In this work, we aim to map a global picture of phase separation and domain formation in membrane of GHUVs by using various copolymers based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEO) with different architectures (grafted, triblock) and molar masses, combined with lipid at fluid (POPC) or gel state (DPPC) at room temperature. From confocal imaging and fluorescence lifetime imaging microscopy technique (FLIM), the phase separation into either micro- or nano- domains within GHVs were studied. In particular, our systematic studies demonstrate that in addition to lipid/polymer fraction or lipid physical state, important factors such as line tension at lipid polymer/lipid boundaries can be finely modulated by the molar mass and architecture of the copolymer and lead to the formation of stable lipid domains with different sizes and morphologies in such GHUVs.

Phase separation in hybrid polymer/lipid giant unillamelar vesicles (GHUVs) has been described over the last few years. However there is still a lack of understanding in physical and molecular factors governing the phase separation in such systems. Among these parameters it has been suggested that in analogy to multicomponent lipid vesicles that hydrophobic mismatchs as well as lipid fludity play a role.In this work, we aim to map a global picture of phase separation and domain formation in membrane of GHUVs by using various copolymers based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEO) with different architectures (grafted, triblock) and molar masses, combined with lipid at fluid (POPC) or gel state (DPPC) at room temperature. From confocal imaging and fluorescence lifetime imaging microscopy technique (FLIM), the phase separation into either micro- or nano- domains within GHVs were studied. In particular, our systematic studies demonstrate that in addition to lipid/polymer fraction or lipid physical state, important factors such as line tension at lipid polymer/lipid boundaries can be finely modulated by the molar mass and architecture of the copolymer and lead to the formation of stable lipid domains with different sizes and morphologies in such GHUVs.

New graft glycopolymers with well-defined parameters [dextran-g-poly(diethylene glycol cholesteryl ether acrylate) (Dex-g-PADEGChol)] have been prepared in four steps using the "grafting from" strategy. Challenge of this work arises from the combination for the first time of a hydrophilic, biocompatible/biodegradable polysaccharide backbone with mesogen hydrophobic polymeric grafts. Controlled growth of the grafts (PADEGChol) was obtained using ATRP initiated in homogeneous medium from a dextran derivative (DexAcBr). In order to find the best polymerization conditions, homopolymerization of ADEGChol monomer was investigated using an initiator model and various catalytic systems CuIBr/(PMDETA or OPMI) in two solvents (Toluene and THF). The amphiphilic properties of such glycopolymers were evaluated and their mesomorphic properties have been studied by thermal polarizing optical microscopy, differential scanning calorimetry and X-ray scattering. Using transmission electron microscopy and dynamic light scattering, vesicular morphology called "polymersome" was observed in aqueous medium when DMSO was used as co-solvent. These polymersomes could be tested as new drug delivery systems; De nouveaux glycopolymères greffés aux paramètres macromoléculaires contrôlés [dextrane-g-poly(acrylate de diéthylène glycol cholestéryle), Dex-g-PADEGChol] ont été préparés en quatre étapes via la stratégie de synthèse « grafting from». L'originalité de ces glycopolymères réside dans la combinaison, et pour la première fois, d'une dorsale polysaccharide hydrophile biocompatible/ biodégradable et de greffons polymères hydrophobes à caractère mésogène. L'ATRP a été utilisée pour contrôler la croissance des greffons PADEGChol en milieu homogène à partir d'un macroamorceur dérivé de dextrane (DexAcBr). Les conditions de polymérisation avaient été préalablement ajustées en étudiant l'homopolymérisation du monomère ADEGChol en présence d'un amorceur modèle et de plusieurs systèmes catalytiques CuIBr/(PMDETA ou OPMI) dans différents solvants (THF ou toluène). Le caractère amphiphile de ces glycopolymères a été évalué et leurs propriétés mésomorphes ont été étudiées par calorimétrie différentielle à balayage, microscopie optique à lumière polarisante et par diffraction des rayons X. Des études préliminaires par microscope électronique à transmission et diffusion dynamique de la lumière polarisée ont démontré que ces glycopolymères adoptent une morphologie vésiculaire appelée « polymersome » en phase aqueuse, lorsque le DMSO est utilisé comme co-solvant. Ces nano-objets pourront être testés ultérieurement pour la formulation d'un nouveau type de vecteurs de principes actifs

New graft glycopolymers with well-defined parameters [dextran-g-poly(diethylene glycol cholesteryl ether acrylate) (Dex-g-PADEGChol)] have been prepared in four steps using the "grafting from" strategy. Challenge of this work arises from the combination for the first time of a hydrophilic, biocompatible/biodegradable polysaccharide backbone with mesogen hydrophobic polymeric grafts. Controlled growth of the grafts (PADEGChol) was obtained using ATRP initiated in homogeneous medium from a dextran derivative (DexAcBr). In order to find the best polymerization conditions, homopolymerization of ADEGChol monomer was investigated using an initiator model and various catalytic systems CuIBr/(PMDETA or OPMI) in two solvents (Toluene and THF). The amphiphilic properties of such glycopolymers were evaluated and their mesomorphic properties have been studied by thermal polarizing optical microscopy, differential scanning calorimetry and X-ray scattering. Using transmission electron microscopy and dynamic light scattering, vesicular morphology called "polymersome" was observed in aqueous medium when DMSO was used as co-solvent. These polymersomes could be tested as new drug delivery systems, De nouveaux glycopolymères greffés aux paramètres macromoléculaires contrôlés [dextrane-g-poly(acrylate de diéthylène glycol cholestéryle), Dex-g-PADEGChol] ont été préparés en quatre étapes via la stratégie de synthèse « grafting from». L'originalité de ces glycopolymères réside dans la combinaison, et pour la première fois, d'une dorsale polysaccharide hydrophile biocompatible/ biodégradable et de greffons polymères hydrophobes à caractère mésogène. L'ATRP a été utilisée pour contrôler la croissance des greffons PADEGChol en milieu homogène à partir d'un macroamorceur dérivé de dextrane (DexAcBr). Les conditions de polymérisation avaient été préalablement ajustées en étudiant l'homopolymérisation du monomère ADEGChol en présence d'un amorceur modèle et de plusieurs systèmes catalytiques CuIBr/(PMDETA ou OPMI) dans différents solvants (THF ou toluène). Le caractère amphiphile de ces glycopolymères a été évalué et leurs propriétés mésomorphes ont été étudiées par calorimétrie différentielle à balayage, microscopie optique à lumière polarisante et par diffraction des rayons X. Des études préliminaires par microscope électronique à transmission et diffusion dynamique de la lumière polarisée ont démontré que ces glycopolymères adoptent une morphologie vésiculaire appelée « polymersome » en phase aqueuse, lorsque le DMSO est utilisé comme co-solvant. Ces nano-objets pourront être testés ultérieurement pour la formulation d'un nouveau type de vecteurs de principes actifs

International audience; A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGCholA), has been successfully polymerized by atom transfer radical polymerization (ATRP) for the first time. Appropriate experimental conditions to control the polymerization of DEGCholA have been investigated using a model initiator (ethyl 2-bromoisobutyrate) in tetrahydrofuran (THF) or toluene at 60 degrees C. Well-controlled ATRP of DEGCholA was obtained using N,N,N',N',N `'-pentamethyldiethylenetriamine as ligand in THF at 60 degrees C. These conditions were then applied to initiate the ATRP of DEGCholA from multifunctional macroinitiators based on dextran. Using a protection/deprotection synthetic scheme, novel graft glycopolymers (Dex-g-PDEGCholA) have been synthesized. The mesomorphic properties of DEGCholA, PDEGCholA, and Dex-g-PDEGCholA have been studied by thermal polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering. PDEGCholA and Dex-g-PDEGCholA show an interdigitated smectic A phase (SmAd) between T-g (similar to 30 degrees C) and around 170 degrees C.