Hydration forces at solid and fluid biointerfaces

We review the different molecular mechanisms giving rise to the repulsive hydration force between biologically relevant surfaces such as lipid bilayers and bio-ceramics. As we will show, the hydration force manifests itself in very different and subtle ways depending on the substrates. Soft, mobile surfaces such as lipid bilayers tend to exhibit monotonic, decaying hydration force, originated from the entropic constriction of the lipid head groups. Solid surfaces on the other hand, tend to exhibit a periodic oscillatory hydration force, originated from the surface induced polarization of water molecules. In this review we will describe both subtle faces of this important interaction by first describing the early experiments performed on solid surfaces and their interpretation by recent simulation studies. Then we will describe the hydration force between fluid interfaces such as bilayers and explain how experimentally researchers have unraveled the dominant role of the lipid head groups conformation

Mechanistic insights into the directed assembly of hydrogel blocks mediated by polyelectrolytes or microgels

In this study, we report the directed assembly of hydrogel blocks mediated by electrostatic interactions. We compared two different assembly mechanisms, one mediated by microgel particles and another mediated by direct interaction between oppositely charged blocks. The system consisted of hydrogel blocks made of an interpenetrated network of (hydroxyethyl)methacrylate-poly(ethylene glycol)dimethacrylate (HEMA-PEGDMA) and either positively charged polyethylenimine (PEI) or negatively charged hyaluronic acid (HA). Positively charged hydrogel blocks were pretreated with negatively charged microgel particles (MG) made of N-isopropylacrylamide-methacrylic acid. Both systems (PEI/HA and PEI/MG) demonstrated spontaneous directed assembly, meaning that positive blocks were systematically found in contact with oppositely charged blocks. Directed assembly in water of PEI/HA blocks resulted in large and open aggregates, while PEI/MG blocks exhibited more compact aggregates. Effects of salt and pH were also assessed for both systems. Inhibition of blocks aggregation was found to appear above a critical salt concentration (CSalt*) which was significantly higher for the PEI/HA system (80 mM) compared to the PEI/MG system (5-20 mM). The observed difference was interpreted in terms of the nanostructure of the contact area between blocks. Blocks aggregation was also found to be controlled by the content of negatively charged groups in the microgels as well as the concentration of MG in the suspension (CMG) used to treat the hydrogel block surfaces. Our results shine light on the subtle differences underlying the adhesion mechanisms between hydrogel blocks and suggest new routes toward the design of innovative complex soft materials

Etude des propriétés physicochimiques des vecteurs nanoparticulaires

Cette thèse rapporte l’étude des propriétés physicochimiques des nanoparticles polymériques et leur impact sur l’interaction avec les cellules vivantes. Nous nous sommes tout spécialement attachés à étudier l’effet des propriétés adhésives et mécaniques des nanoparticules sur leur capacité de pénétration de la membrane cellulaire. Pour ce faire, nous avons tout d’abord utilisé des nanoparticules d’acide polylactique (PLA) fonctionnalisées en surface avec un ligand des sélectines E et P. Le greffage du ligand sur la particule s’est fait par une nouvelle méthode expérimentale garantissant la présence du ligand à la surface de la particule durant toute sa durée de vie. Cette méthode consiste à mélanger un polymère fonctionnalisé avec le ligand avec un autre polymère non fonctionnalisé. La présence du ligand à la surface des nanoparticules formées à partir de ce mélange de polymères a été confirmée par analyse ToF SIMS. Nous avons pu prouver que les particules possédant le ligand greffé à leur surface démontraient une capacité adhésive supérieure à leurs homologues non fonctionnalisés sur des cellules endothéliales HUVEC activées par différentes drogues. De plus, le captage des particules par les cellules HUVEC est modulé par le niveau d’expression des récepteurs selectine E et P et aussi par la quantité de ligand libre. Ces résultats montrent clairement que le greffage du ligand confère aux particules des propriétés adhésives accrues et spécifiques ce qui permet leur usage postérieure comme vecteur pharmaceutique capable de cibler un récepteur particulier à la surface d’une cellule. Nous avons aussi démontré que l’interaction entre les nanoparticules et la membrane cellulaire peut aussi être contrôlée aussi bien par les propriétés mécaniques de la cellule que de la nanoparticule. Dans une première étape, nous avons mesuré à l’aide de l’appareil de forces de surface l’élasticité de cellules macrophagiques déposées sur différents substrats. En contrôlant l’interaction entre la cellule et le substrat sur lequel elle repose nous avons montré qu’il était possible de modifier à ii volonté les propriétés mécaniques cellulaire. Une augmentation de l’élasticité cellulaire s’accompagne d’une augmentation systématique de l’internalisation de nanoparticules de PLA non fonctionnalisées. Ceci suggère un rôle prépondérant des propriétés mécaniques du cortex cellulaire dans le captage des nanoparticules de PLA. Dans une seconde étape, nous avons étudié l’effet des propriétés mécaniques des nanoparticules sur leur capacité de pénétration cellulaire. Pour ce faire, nous avons synthétisé des particules d’hydrogel dont l’élasticité était contrôlée par le degré d’agent réticulant inclus dans leur formulation. Le contrôle des propriétés mécaniques des nanoparticules a été confirmé par la mesure du module de Young des particules par microscopie de force atomique. L’impact des propriétés mécaniques de ces particules sur leur capacité de pénétration dans les cellules vivantes a été étudié sur des cellules macrophagiques de souris. Les résultats ont montré que la cinétique d’internalisation, la quantité de particules internalisées et le mécanisme d’internalisation dépendent tous du module de Young des nanoparticules. Aucune différence dans le trajet intracellulaire des particules n’a pu être observée malgré le fait que différentes voies d’internalisation aient été observées. Ce dernier résultat peut s’expliquer par le fait que les nanoparticules sont internalisées par plusieurs voie simultanément ce qui facilite leur accumulation dans les organelles digestives intracellulaires. Un modèle simple permettant d’expliquer ces résultats a été proposé et discuté.This thesis reports the study of physical chemical properties of polymeric nanoparticles and their impact on the interaction with living cells. In particular we endeavoured to study the effect of the adhesive and mechanical properties of the vector on its capacity of penetration of the cellular membrane. With this intention, we firstly used nanoparticules of polylactic acid (PLA) functionalized on their surfaces with a ligand of the selectines E and P receptor. The grafting of the ligand on the particle’s surface was carried out thanks to a new experimental method guaranteeing the presence of the active molecule on the surface of the particle during its whole life cycle. This method consists in mixing a polymer functionalized with the ligand with another polymer not functionalized. The presence of the ligand on the surface of the nanoparticules formed starting from this mixture of polymers was confirmed by ToF SIMS analysis. We could show that the particles having the ligand grafted on their surface exhibit a higher adhesive capacity than their non-functionalized counterpart on endothelial cells HUVEC activated by various drugs. Nanoparticles adhesion on cells membrane was modulated by the level of expression of the receptors selectine E and P and also by the quantity of free ligand. These results show clearly that the functionalized particles possess all the characteristics of a pharmaceutical vector capable of targeting a particular receptor on a cell surface. The interaction between nanoparticules and cellular membrane can also be controlled by the mechanical properties of the cell as well as of the nanoparticule. To demonstrate it we have measured the elasticity of macrophagic cells deposited on various substrates using the SFA. We have thus showed that it was possible to control the cell mechanical properties at will by controlling the interaction between the cell and the substrate on which it rests. An increase of the cell elasticity is accompanied by an increase of the internalization of non-functionalized PLA nanoparticules. This suggests a major role of cytocortical mechanical properties in the capture of hard PLA particles. iv Lastly, we studied the effect of the mechanical properties of the nanoparticules on their cellular penetration capacity. With this intention, we synthesized hydrogel particles whose elasticity was controlled by the degree of crosslinking agent included in their formulation. The control of the mechanical properties of the nanoparticules was confirmed by the measurement of the Young modulus of the particles by AFM. The interaction of these particles with macrophagess showed that the mechanical properties of the particles affect various aspects related to the internalization of the nanoparticles. The internalization kinetics, the quantity of internalized particles and the mechanism of internalization depend all on the Young modulus of the nanoparticules. No differences in the intracellular pathway could be observed in spite of the fact that various pathways of internalization were observed for these nanoparticules. This last result can be explained by the fact that the nanoparticules are internalized by several mechanisms of simultaneously which facilitates their accumulation in intracellular digestive organelles. A simple model explaining these results is proposed and discussed

2D, 3D and 4D active compound delivery in tissue engineering and regenerative medicine

Recent advances in tissue engineering and regenerative medicine have shown that controlling cells microenvironment during growth is a key element to the development of successful therapeutic system. To achieve such control, researchers have first proposed the use of polymeric scaffolds that were able to support cellular growth and, to a certain extent, favor cell organization and tissue structure. With nowadays availability of a large pool of stem cell lines, such approach has appeared to be rather limited since it does not offer the fine control of the cell micro-environment in space and time (4D). Therefore, researchers are currently focusing their efforts on developing strategies that include active compound delivery systems in order to add a fourth dimension to the design of 3D scaffolds. This review will focus on recent concepts and applications of 2D and 3D techniques that have been used to control the load and release of active compounds used to promote cell differentiation and proliferation in or out of a scaffold. We will first present recent advances in the design of 2D polymeric scaffolds and the different techniques that have been used to deposit molecular cues and cells in a controlled fashion. We will continue presenting the recent advances made in the design of 3D scaffolds based on hydrogels as well as polymeric fibers and we will finish by presenting some of the research avenues that are still to be explored

Du best-seller aujourd’hui

Rien n’est plus difficile que de pouvoir dire par avance ce que pourront être les ventes d'un livre. Et pourtant il est un éditeur en France qui depuis des années multiplie les succès et qui à ce titre fait un peu figure de M. Best-sellers dans le monde de la culture française — c'est Bernard Fixot. S'il vient d'être quitté avec fracas par Guillaume Musso, c'est peut-être un échec, mais probablement pas le signe d'un déclin ; c'est plutôt la preuve que le reste de l'édition le jalouse et cherche de plus en plus à le concurrencer en adoptant ses méthodes de vente ou ses modes de fonctionnement éditoriaux. Quels sont justement ses recettes ? Comment parvient-il à écouler des centaines de milliers d'exemplaires formatés pour le très grand public ? Qu'est-ce que les succès de Marc Levy ou Guillaume Musso révèlent des goûts ou des pratiques culturelles des Français 

Phytoglycogen nanoparticles : nature-derived superlubricants

Phytoglycogen nanoparticles (PhG NPs), a single-molecule highly branched polysaccharide, exhibit excellent water retention, due to the abundance of close-packed hydroxyl groups forming hydrogen bonds with water. Here we report lubrication properties of close-packed adsorbed monolayers of PhG NPs acting as boundary lubricants. Using direct surface force measurements, we show that the hydrated nature of the NP layer results in its striking lubrication performance, with two distinct confinement-controlled friction coefficients. In the weak- to moderate-confinement regime, when the NP layer is compressed down to 8% of its original thickness under a normal pressure of up to 2.4 MPa, the NPs lubricate the surface with a friction coefficient of 10–3. In the strong-confinement regime, with 6.5% of the original layer thickness under a normal pressure of up to 8.1 MPa, the friction coefficient was 10–2. Analysis of the water content and energy dissipation in the confined NP film reveals that the lubrication is governed by synergistic contributions of unbound and bound water molecules, with the former contributing to lubrication properties in the weak- to moderate-confinement regime and the latter being responsible for the lubrication in the strong-confinement regime. These results unravel mechanistic insights that are essential for the design of lubricating systems based on strongly hydrated NPs

Bioinspired microstructures of chitosan hydrogel provide enhanced wear protection

We describe the fabrication of physical chitosan hydrogels exhibiting a layered structure. This bilayered structure, as shown by SEM and confocal microscopy, is composed of a thin dense superficial zone (SZ), covering a deeper zone (DZ) containing microchannels orientated perpendicularly to the SZ. We show that such structure favors diffusion of macromolecules within the hydrogel matrix up to a critical pressure, σc, above which channels were constricted. Moreover, we found that the SZ provided a higher wear resistance than the DZ which was severely damaged at a pressure equal to the elastic modulus of the gel. The coefficient of friction (CoF) of the SZ remained independent of the applied load with μSZ = 0.38 ± 0.02, while CoF measured at DZ exhibited two regimes: an initial CoF close to the value found on the SZ, and a CoF that decreased to μDZ = 0.18 ± 0.01 at pressures higher than the critical pressure σc. Overall, our results show that internal structuring is a promising avenue in controlling and improving the wear resistance of soft materials such as hydrogels

Effect of polymer architecture on Curcumin 1 encapsulation and release from PEGylated polymer nanoparticles: toward a drug delivery nano-platform to the CNS

We developed a nanoparticles (NPs) library from poly(ethylene glycol)–poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a “micelle-like” or “polymer nano-aggregate” structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to “polymer nano-aggregate” particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers

Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers

The surface forces apparatus and atomic force microscope were used to study the effects of lipid composition and concentrations of myelin basic protein (MBP) on the structure of model lipid bilayers, as well as the interaction forces and adhesion between them. The lipid bilayers had a lipid composition characteristic of the cytoplasmic leaflets of myelin from "normal" (healthy) and "disease-like" [experimental allergic encephalomyelitis (EAE)] animals. They showed significant differences in the adsorption mechanism of MBP. MBP adsorbs on normal bilayers to form a compact film (3-4 nm) with strong intermembrane adhesion (∼0.36 mJ/m(2)), in contrast to its formation of thicker (7-8 nm) swelled films with weaker intermembrane adhesion (∼0.13 mJ/m(2)) on EAE bilayers. MBP preferentially adsorbs to liquid-disordered submicron domains within the lipid membranes, attributed to hydrophobic attractions. These results show a direct connection between the lipid composition of membranes and membrane-protein adsorption mechanisms that affects intermembrane spacing and adhesion and has direct implications for demyelinating diseases

Nanoparticle heterogeneity : an emerging structural parameter 2 influencing particle fate in biological media?

Drug nanocarriers’ surface chemistry is often presumed to be uniform. For instance, the polymer surface coverage and distribution of ligands on nanoparticles are described with averaged values obtained from quantification techniques based on particle populations. However, these averaged values may conceal heterogeneities at different levels, either because of the presence of particle sub-populations or because of surface inhomogeneities, such as patchy surfaces on individual particles. The characterization and quantification of chemical surface heterogeneities are tedious tasks, which are rather limited by the currently available instruments and research protocols. However, heterogeneities may contribute to some non-linear effects observed during the nanoformulation optimization process, cause problems related to nanocarrier production scale-up and correlate with unexpected biological outcomes. On the other hand, heterogeneities, while usually unintended and detrimental to nanocarrier performance, may, in some cases, be sought as adjustable properties that provide NPs with unique functionality. In this review, results and processes related to this issue are compiled, and perspectives and possible analytical developments are discussed