Laboratoire P.A.S.T.E.U.R

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FAST : la start-up de chimie théorique – un nouveau paradigme pour le « drug design » !

FAST est une start-up localisée au sein du Département de Chimie de l’ENS proposant une solution logicielle pour calculer et visualiser en 3D les interactions entre l’eau et n’importe quelle molécule, médicament ou protéine et donc réduire les coûts de conception et accélérer la sélection de molécules thérapeutiques en drug design.

Protein Adsorption and Reorganization on Nanoparticles Probed by the Coffee- Ring Effect: Application to Single Point Mutation Detection

J. Am. Chem. Soc 2016, 138, 11623–11632


The coffee-ring effect denotes the accumulation of particles at the edge of an evaporating sessile drop pinned on a substrate. Because it can be detected by simple visual inspection, this ubiquitous phenomenon can be envisioned as a robust and cost-effective diagnostic tool. Toward this direction, here we systematically analyze the deposit morphology of drying drops containing polystyrene particles of different surface properties with various proteins (bovine serum albumin (BSA) and diff erent forms of hemoglobin). We show that deposit patterns reveal information on both the adsorption of proteins onto particles and their reorganization following adsorption. By combining pattern analysis with adsorption isotherm and zeta potential measurements, we show that the suppression of the coffee-ring effect and the formation of a disk-shaped pattern is primarily associated with particle neutralization by protein adsorption. However, our fi ndings also suggest that protein reorganization following adsorption can dramatically invert this tendency. Exposure of hydrophobic (respectively charged) residues can lead to disk (respectively ring) deposit morphologies independently of the global particle charge. Surface tension measurements and microscopic observations of the evaporating drops show that the determinant factor of the deposit morphology is the accumulation of particles at the liquid/gas interface during evaporation. This general behavior opens the possibility to probe protein adsorption and reorganization on particles by the analysis of the deposit patterns, the formation of a disk being the robust signature of particles rendered hydrophobic by protein adsorption. 


Ultrafast Dynamics of a Green Fluorescent Protein Chromophore Analogue: Competition between Excited-State Proton Transfer and Torsional Relaxation

J. Phys. Chem. B2016120 (36), pp 9716–9722


The competition between excited-state proton transfer (ESPT) and torsion plays a central role in the photophysics of fluorescent proteins of the green fluorescent protein (GFP) family and their chromophores. Here, it was investigated in a single GFP chromophore analogue bearing o-hydroxy and p-diethylamino substituents, OHIM. The light-induced dynamics of OHIM was studied by femtosecond transient absorption spectroscopy, at different pH. We found that the photophysics of OHIM is determined by the electron-donating character of the diethylamino group: torsional relaxation dominates when the diethylamino group is neutral, whereas ultrafast ESPT followed by cis/trans isomerization and ground-state reprotonation are observed when the diethylamino group is protonated and therefore inactive as an electron donor.

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

Nanoscale, 2016, 8, 14530


Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell–medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi-electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses.


Nanometric emulsions encapsulating solid particles as alternative carriers for intracellular delivery

In the current study we developed a multi-functional platform based on oil-in-water emulsions. These nano-vehicles (360 nm) are composed of an edible oil core stabilised by a biocompatible surfactant and encapsulate hydrophobic-functionalised silica nanoparticles (60 nm). The concept is depicted in Figure 1. The silica nanoparticles were rendered fluorescent by covalent grafting to use fluorescence microscopy to track the particles during cell studies. After characterisation, the particles were incubated with model epithelial cells HeLa to determine the effect of solid particles encapsulation within an oil droplet on their interaction with the cells, their internalisation pathway and subsequent intracellular fate as compared to free solid nanoparticles.