Fabien Picaud

New bioinspired membrane made of a biological ion channel confined into the cylindrical nanopore of a solid-state polymer.

A hybrid nanoporous membrane made of a solid-state polymeric thin film in which an ion channel is confined is realized. The primary and extremely encouraging results obtained by confocal fluorescence spectroscopy and ion diffusion measurement demonstrate respectively that (i) the considered ion channel, that is, Gramicidin-A, can be confined selectively inside the nanopores and (ii) the ionic permeability of the membrane is enhanced. Atomistic molecular simulations are also reported and fruitfully compared to the experimental findings.

Influence of molecular adsorption on the dielectric properties of a single wall nanotube: a model sensor.

Recent measurements of the resonance frequency of a copper disk covered with carbon nanotube bundles have shown characteristic resonance shifts during exposure with various gas molecules. The shifts were interpreted as the change of the dielectric permittivity of the system forming the sensor due to the electric properties of the adsorbed molecules. Starting from a simplified sensor model formed by one single wall nanotube, we develop a self-consistent approach to describe the variation of the linear dielectric susceptibility of the tube at the atomic scale when molecules are adsorbed at its external surface. The sensitivity of this model sensor is tested as a function of the apolar or polar nature of the admolecules, their adsorption geometry, their concentration, and the characteristics of the tube (length, diameter,...). The comparison with data on dielectric constant changes vs adsorption, coming from measurements of the resonance frequency shifts, displays striking agreement for most of the molecular species considered.

Gas-induced variation in the dielectric properties of carbon nanotube bundles for selective sensing

There is an increasing demand for robust, miniaturized sensors with ppm or parts per 109(ppb) sensing capability, and high selectivity to different chemical or biological species. Here we show that trace amounts (ppb) of gases or organic solvent vapors can be detected with high selectivity and sensitivity using single-walled carbon nanotube bundles in a resonator configuration. The enhanced sensing properties result from a change in the effective dielectric properties of the resonator when exposed to different gas environments. A theoretical model is described which computes resonant frequency shifts that are in remarkable agreement with corresponding experimental shifts exhibited by the resonator when exposed to different gas molecules. This work demonstrates a gas-sensing platform with superior sensitivity and selectivity for gas detection, and presents advantages in terms of portability and recovery time. In particular, the sensing platform does not require functionalized carbon nanotubes to enhance sp...

Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20-fold in different Human tumor cell lines including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

Targeted molecular dynamics of an open-state KcsA channel

Pore opening of KcsA channel is studied using targeted molecular dynamics simulations. Conformational changes of the protein are determined, starting from the crystallized refined 2.0 A structure (pdb 1K4C) determined in x-ray experiments and arriving to the open-state structure constructed on the basis of electron paramagnetic resonance spectroscopic data (pdb 1JQ1). Our results corroborate the essential role played by the terminal residues located on the transmembrane helices M2 which were not taken into account at that time. The aperture mechanism of the channel appears to be ziplike. A small constraint (approximately equal to 5 x 10(-2) kcal mol(-1) A(-2) per C(alpha)) applied to the terminal residues located on the intracellular side is sufficient to initialize the pore opening at the innermost part of the gate, but additional constraint must be applied to definitely complete the pore aperture. The open structure is proved to be a metastable state since releasing the constraint leads to another relaxed open conformation which seems to reach stability.

Encapsulation into Carbon Nanotubes and Release of Anticancer Cisplatin Drug Molecule

Molecular dynamics simulations have been investigated to study the interactions between single-wall carbon nanotubes and an anticancer agent Pt complex (Cisplatin). The optimized diameter of the vector system has been determined to encapsulate in the best conditions the drug molecules. The simulation results show also that several drug molecules can be adsorbed inside the nanotubes, leading to an increased confinement time. Moreover, our simulations show that the release of the drug near a cell membrane model is favored, opening the way to a natural drug nanocapsule.

Chiral response of single walled carbon nanotube based sensors to adsorption of amino acids: A theoretical model

Calculations of the interaction energy and dielectric responses of chiral single walled carbon nanotubes to the presence of amino acid enantiomers are carried out. A theoretical study is developed to show that the frequency shifts of selected nanotubes conveniently tailored to the size of the probed molecules and used in a resonator configuration can selectively detect different species of amino acids and the left- and right-handed enantiomers of these species. Criteria for an optimization of the adsorption energy and frequency response on the size and chiral angle of the nanotubes are given. It is found that a very small set of carbon tubes obeys these conditions.

Ionic transport through sub-10 nm diameter hydrophobic high-aspect ratio nanopores: experiment, theory and simulation

Fundamental understanding of ionic transport at the nanoscale is essential for developing biosensors based on nanopore technology and new generation high-performance nanofiltration membranes for separation and purification applications. We study here ionic transport through single putatively neutral hydrophobic nanopores with high aspect ratio (of length L = 6 μm with diameters ranging from 1 to 10 nm) and with a well controlled cylindrical geometry. We develop a detailed hybrid mesoscopic theoretical approach for the electrolyte conductivity inside nanopores, which considers explicitly ion advection by electro-osmotic flow and possible flow slip at the pore surface. By fitting the experimental conductance data we show that for nanopore diameters greater than 4 nm a constant weak surface charge density of about 10−2 C m−2 needs to be incorporated in the model to account for conductance plateaus of a few pico-siemens at low salt concentrations. For tighter nanopores, our analysis leads to a higher surface charge density, which can be attributed to a modification of ion solvation structure close to the pore surface, as observed in the molecular dynamics simulations we performed.

N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.

Boron Nitride Nanoporous Membranes with High Surface Charge by Atomic Layer Deposition

In this work, we report the design and the fine-tuning of boron nitride single nanopore and nanoporous membranes by atomic layer deposition (ALD). First, we developed an ALD process based on the use of BBr3 and NH3 as precursors in order to synthesize BN thin films. The deposited films were characterized in terms of thickness, composition, and microstructure. Next, we used the newly developed process to grow BN films on anodic aluminum oxide nanoporous templates, demonstrating the conformality benefit of BN prepared by ALD, and its scalability for the manufacturing of membranes. For the first time, the ALD process was then used to tune the diameter of fabricated single transmembrane nanopores by adjusting the BN thickness and to enable studies of the fundamental aspects of ionic transport on a single nanopore. At pH = 7, we estimated a surface charge density of 0.16 C·m-2 without slip and 0.07 C·m-2 considering a reasonable slip length of 3 nm. Molecular dynamics simulations performed with experimental conditions confirmed the conductivities and the sign of surface charges measured. The high ion transport results obtained and the ability to fine-tune nanoporous membranes by such a scalable method pave the way toward applications such as ionic separation, energy harvesting, and ultrafiltration devices.