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Understanding the mechanisms underlying amyloid-β (Aβ) aggregation is pivotal in the context of Alzheimer's disease. This study aims to elucidate the secondary nucleation process of Aβ42 peptides by combining experimental and computational methods. Using a newly developed nanopipette-based amyloid seeding and translocation assay, confocal fluorescence spectroscopy, and molecular dynamics simulations, the influence of the seed properties on Aβ aggregation is investigated. Both fragmented and unfragmented seeds played distinct roles in the formation of oligomers, with fragmented seeds facilitating the formation of larger aggregates early in the incubation phase. The results show that secondary nucleation leads to the formation of oligomers of various sizes and structures as well as larger fibrils structured in β-sheets. From these findings a mechanism of secondary nucleation involving two types of aggregate populations, one released and one growing on the mother fiber is proposed., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Polytetrafluoroethylene (PTFE) and, by extension, fluoropolymers are ubiquitous in science, life, and the environment as perfluoroalkyl pollutants (PFAS). In all cases, it is difficult to transform these materials due to their chemical inertness. Herein, we report a direct amination process of PTFE and some fluoropolymers such as polyvinylidene fluoride (PVDF) and Nafion by lithium alkylamide salts. Synthesizing these reactants extemporaneously between lithium metal and an aliphatic primary di- or triamine that also serves as a solvent leads to the rapid nucleophilic substitution of fluoride by an alkylamide moiety when in contact with the fluoropolymer. Moreover, lithium alkylamides dissolved in suitable solvents other than amines can react with fluoropolymers. This highly efficient one-pot process opens the way for further surface or bulk modification if needed, providing an easy, inexpensive, and fast experiment protocol on large scales.

Nanofluidics has a very promising future owing to its numerous applications in many domains. It remains, however, very difficult to understand the basic physico-chemical principles that control the behavior of solvents confined in nanometric channels. Here, water and ion transport in carbon nanotubes is investigated using classical force field molecular dynamics simulations. By combining one single walled carbon nanotube (uniformly charged or not) with two perforated graphene sheets, we mimic single nanopore devices similar to experimental ones. The graphitic edges delimit two reservoirs of water and ions in the simulation cell from which a voltage is imposed through the application of an external electric field. By analyzing the evolution of the electrolyte conductivity, the role of the carbon nanotube geometric parameters (radius and chirality) and of the functionalization of the carbon nanotube entrances with OH or COO - groups is investigated for different concentrations of group functions.

The cisplatin encapsulation into carbon nanohorns (CNH) is a promising nanoformulation to circumvent the drug dissipation and to specifically accumulate it in tumor sites. Herein, biased molecular dynamics simulations were used to analyze the transmembrane transport of the CNH loaded with cisplatin through a breast cancer cell membrane prototype. The simulations revealed a four-stage mechanism: approach, insertion, permeation, and internalization. Despite the lowest structural disturbance of the membrane provided by the nanocarrier, the average free energy barrier for the translocation was 55.2 kcal mol -1 , suggesting that the passive process is kinetically unfavorable. In contrast, the free energy profiles revealed potential wells of -6.8 kcal mol -1 along the insertion stage in the polar heads region of the membrane, which might enhance the retention of the drug in tumor sites; therefore, the most likely cisplatin delivery mechanism should involve the adsorption and retention of CNH on the surface of cancer cells, allowing the loaded cisplatin be slowly released and passively transported through the cell membrane.

Breast cancer is one of the most frequent modalities of cancer worldwide, with notable mortality. The medication based on platinum drugs (cisplatin (cddp), carboplatin (cpx), and oxaliplatin (oxa)) is a conventional chemotherapy despite severe side effects and the development of drug resistance. In order to provide a deeper molecular description of the influx and efflux processes of platinum drugs through breast cancer tissues, this study focuses on molecular dynamics (MD) simulations of the passive translocation process through a realistic plasma membrane prototype of human breast cancer cell (c_memb). The results showed that the permeation events were mainly mediated by neutral lipids (DOPC, DOPE, and cholesterol), producing a low and temporary membrane deformation. The drug insertion in the region of polar heads was the most favorable stage of the translocation mechanism, especially for cddp and oxa with potential wells of -8.6 and -9.8 kcal mol -1 , respectively. However, the potentials of mean force (PMF) revealed unfavorable kinetics for the permeation of these drugs through lipid tails, with energy barriers of 28.3 (cddp), 32.2 (cpx), and 30.4 kcal mol -1 (oxa). The low permeability coefficients ( P ) of cpx and oxa, which were 3 and 1 orders of magnitude inferior than for cddp, resulted from the high energy barriers for their traslocation processes through the membrane. The obtained results provide a more accurate picture of the permeation of Pt(II)-based drugs through breast cancer cells, which may be relevant for the design and evaluation of new platinum complexes.

In this work, early-stage Aβ42 aggregates were detected using a real-time fast amyloid seeding and translocation (RT-FAST) assay. Specifically, Aβ42 monomers were incubated in buffer solution with and without preformed Aβ42 seeds in a quartz nanopipette coated with L-DOPA. Then, formed Aβ42 aggregates were analyzed on flyby resistive pulse sensing at various incubation time points. Aβ42 aggregates were detected only in the sample with Aβ42 seeds after 180 min of incubation, giving an on/off readout of the presence of preformed seeds. Moreover, this RT-FAST assay could detect preformed seeds spiked in 4% cerebrospinal fluid/buffer solution. However, in this condition, the time to detect the first aggregates was increased. Analysis of Cy3-labeled Aβ42 monomer adsorption on a quartz substrate after L-DOPA coating by confocal fluorescence spectroscopy and molecular dynamics simulation showed the huge influence of Aβ42 adsorption on the aggregation process.

Ivermectin is an antiparasitic drug that results in the death of the targeted parasites using several mechanical actions. While very well supported, it can induce in rare cases, adverse effects including coma and respiratory failure in case of overdose. This problem should be solved especially in an emergency situation. For instance, the first pandemic of the 21th century was officially declared in early 2020, and while several vaccines around the worlds have been used, an effective treatment against this new strain of coronavirus, better known as SARS-CoV-2, should also be considered, especially given the massive appearance of variants. From all the tested therapies, Ivermectin showed a potential reduction of the viral portability, but sparked significant debate around the dose needed to achieve these positive results. To answer this general question, we propose, using simulations, to show that the nanovectorization of Ivermectin on BN oxide nanosheets can increase the transfer of the drug to its target and thus decrease the quantity of drug necessary to cope with the disease. This first application could help science to develop such nanocargo to avoid adverse effects.Communicated by Ramaswamy H. Sarma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is nowadays envisaged as a natural cytokine useful in nanomedicine to eradicate the cancer cells and not the healthy surrounding ones. However, it suffers from cell resistance and strong dispersion in body to prove its efficiency. The understanding at the molecular level of the TRAIL interaction with death receptors (DRs) on cancer cells is thus of fundamental importance to improve its action. We demonstrate here via molecular simulations that TRAIL can bind to its both agonistic DRs (ie, DR4 and DR5) with a preference for DR4. In this study, the role of a graphene nanoflake as a potential cargo for TRAIL is examined. Furthermore, both TRAIL self-assembling and TRAIL affinity when adsorbed on graphene are considered to enhance efficacy toward the targeted cancer cell. Our modelization results show that TRAIL can bind to DR4 and DR5 when transported by graphene nanoflake, as a proof of concept., (© 2019 Wiley Periodicals, Inc.)

Solid-state nanopores are an emerging technology used as a high-throughput, label-free analytical method for the characterization of protein aggregation in an aqueous solution. In this work, we used Levodopamine to coat a silicon nitride nanopore surface that was fabricated through a dielectric breakdown in order to reduce the unspecific adsorption. The coating of inner nanopore wall by investigation of the translocation of heparin. The functionalized nanopore was used to investigate the aggregation of amyloid-β and α-synuclein, two biomarkers of degenerative diseases. In the first application, we demonstrate that the α-synuclein WT is more prone to form dimers than the variant A53T. In the second one, we show for the Aβ(42)-E22Δ (Osaka mutant) that the addition of Aβ(42)-WT monomers increases the polymorphism of oligomers, while the incubation with Aβ(42)-WT fibrils generates larger aggregates., (© 2022 The Authors. Chemistry - An Asian Journal published by Wiley-VCH GmbH.)

The Aβ(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the Aβ(1-42) fibril formation in the presence of pyrimethanil, a widely used fungicide belonging to the anilinopyrimidine class. Our results evidenced a pro-aggregating effect of pyrimethanil on Aβ(1-42). Aβ(1-42) assemblies were successfully detected using conical nanopore coated with PEG. Using an analytical model, the large current blockades observed (>0.7) were assigned to species with size close to the sensing pore. The long dwell times (hundreds ms scale) were interpreted by the possible interactions amyloid/PEG using molecular dynamic simulation. Such interaction could leave until splitting phenomena of the dimer structure. Our work also evidences that the pyrimethanil induce an aggregation of Aβ(1-42) mechanism in two steps including the reorganization prior the elongation phase., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood. Nanopore technology provides a new way to obtain kinetic and morphological aspects of Aβ aggregation at a single-molecule scale without labeling by detecting the electrochemical signal of the peptides when they pass through the hole. Here, we investigate the influence of nanoscale geometry (conical and bullet-like shape) of a track-etched nanopore pore and the effect of molecular crowding (polyethylene glycol-functionalized pores) on Aβ fibril sensing and analysis. Various Aβ fibril samples that differed by their length were produced by sonication of fibrils obtained in the presence of epigallocatechin gallate. The conical nanopore functionalized with polyethylene glycol (PEG) 5 kDa is suitable for discrimination of the fibril size from relative current blockade . The bullet-like-shaped nanopore enhances the amplitude of the current and increases the dwell time, allowing us to well discern the fibrils. Finally, the nanopore crowded with PEG 20 kDa enhances the relative current blockade and increases the dwell time; however, the discrimination is not improved compared to the "bullet-shaped" nanopore.

Sorting diameter and handedness of carbon nanotubes still appears as an important challenge in nanotechnology. In this context, supramolecular structures formed by self-assembled chiral molecules deposited on well-defined metal surfaces can be used to discriminate the two isomers of carbon nanotubes. Calculations are carried out to determine the adsorption energy of nanotube enantiomers on alaninate coated Cu(110) surface. The results show a significant discrimination of the L and R handed isomers by such a surface and an additional selectivity in terms of small and large tube diameters. [ABSTRACT FROM AUTHOR]

We study a large sampling of chiral double-wall carbon nanotubes to propose simple formula describing the dependence of the interwall energy, the chiral discrimination energy, and the radial breathing mode frequencies as a function of the main characteristics of the tubes, i.e., their radius, length and chiral angle. It is shown that tube pairs with the same handedness are more stable than enantiomeric pairs, and this discrimination, though small, mainly occurs in the first step of the growth of an inner tube inside an outer one. Chiral splittings of the breathing mode frequencies for the two DWCNT diastereoisomers (ni,mi)@(no,mo) and (mi,ni)@(no,mo) can reach a few wave numbers. [ABSTRACT FROM AUTHOR]

The selective detection of amino acid enantiomers can be achieved by considering chiral nanotubes used in a resonator configuration. We show that this enantioselectivity is appreciably increased when a peptide molecule is inserted in the tube. The chiral polarization of the nanotube at the linear and nonlinear levels due to the inserted polar peptide is very sensitive to the adsorption of left- or right-handed alanine molecules. This leads to a difference in the resonance frequency of the sensor which can increase to 12 MHz when the nanotube is not chiral (instead of 0 for the bare tube) and can reach 38 MHz for a chiral tube (instead of 14 MHz for the bare tube). The influence of the various parameters which are responsible for such a differential frequency shift, i.e., the tube hyperpolarizability, the polar electric properties of the peptide, and the screening effect due to the tube on the peptide-alanine interactions, is discussed and some general rules are given regarding the optimization of the enantioselectivity of these sensors. [ABSTRACT FROM AUTHOR]

We interpret the measured sensitivity difference of single walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) used as dielectric sensors of ammonia gas traces in terms of adsorption sites and effective coverages. The dielectric constant of a regular set of SWNTs deposited on a plane is compared to that of a single MWNT having the same size when the same pressure of ammonia molecules is applied on them. The corresponding resonance frequency shifts in the two sensors display an enhanced sensitivity of SWNT over the MWNT in excellent agreement with the experimental measurements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Based on the formalisms of Langmuir and Fowler, theoretical adsorption isotherms are calculated for different bundle geometries of single wall carbon nanotubes in a triangular lattice. The authors show the dependence of the adsorption properties on the nanotube diameter and on the specific morphology of the bundles they constitute. The authors demonstrate how isotherm curve analysis can help to experimentally determine what kinds of tubes form a given bundle and the ratio of open to closed tubes in a sample having undergone a complete or incomplete opening protocol. In spite of the model’s simplicity, quite satisfactory agreement is observed between experiments and the authors’ calculations. [ABSTRACT FROM AUTHOR]

A semicontinuum approach on the basis of an effective polarizability tensor per length and radius units is used to describe the dielectric response of a long single wall nanotube to the adsorption of an extended molecule. Changes in the permittivity ratio of the nanotube+molecule over the nanotube alone, which are directly connected to frequency shifts of the nanotube in a resonator configuration due to the presence of the molecule, provide a test of sensitivity of the system. The behavior of this ratio is analyzed for linear and circular geometries of the molecule, as a function of the tube characteristics (length and radius) and of the molecular size and polarizability distribution. Extension to three dimensional systems with a large set of polarizable centers is discussed in terms of self-polarization of the centers and morphology of the surface of the sensed system. [ABSTRACT FROM AUTHOR]

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 specificity, or wire connection to the nanotubes making it attractive for remote sensor technology. [ABSTRACT FROM AUTHOR]

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. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Since 2020, the world is facing the first global pandemic of 21st century. Among all the solutions proposed to treat this new strain of coronavirus, named SARS-CoV-2, the vaccine seems a promising way but the delays are too long to be implemented quickly. In the emergency, a dual therapy has shown its effectiveness but has also provoked a set of debates around the dangerousness of a particular molecule, hydroxychloroquine. In particular, the doses to be delivered, according to the studies, were well beyond the acceptable doses to support the treatment without side effects. We propose here to use all the advantages of nanovectorization to address this question of concentration. Using quantum and classical simulations we will show in particular that drug transport on boron nitrogen oxide nanosheets increases the effectiveness of the action of these drugs. This will definitely allow to decrease the drug quantity needing to face the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Solid-state nanopores are a promising platform for characterizing proteins. In order to improve their lifetime and prevent fouling, Polyethylene Glycol (PEG) grafting is one of the most efficient and low-cost solutions. Different models to calculate the PEG thickness do not consider their interaction with the nanopore inner surface nor the effect of confinement. Here, we investigate by molecular dynamic simulation the PEG conformation inside a nanopore in the case of hydrophobic and hydrophilic nanopores. Our results reveal that the nanopore inner surface plays a role in the PEG organization and, thus, in the speed of the salt constituent. The resulting pair interaction between PEG and its environment clearly shows a more important affinity for K + compared to Li + cations.

Several mechanisms for the electropolymerization of pyrrole have been proposed since the first report 40 years ago. However, none of them were consensual despite a range of assumptions. We simulated and explained the preliminary steps governing the electropolymerization of pyrrole in a charged model interface using first-principles molecular dynamics calculations to solve the problem. We have shown under these conditions that adjacent pyrrole molecules in water can react together, causing their electropolymerization at the interface with a biased platinum electrode in anodic oxidation. In this work, the effective screening medium method that prevents energy divergence of the system was applied to different configurations of pyrrole, water, and electrolyte molecules to best screen the phase space. Furthermore, we worked on a Pt(100) electrode surface in an aqueous electrolyte to be as close as possible to the experimental conditions, MD taking the average of their different orientations.

In recent years and with the achievement of nanotechnologies, the development of experiments based on carbon nanotubes has allowed to increase the ionic permeability and/or selectivity in nanodevices. However, this new technology opens the way to many questionable observations, to which theoretical work can answer using several approximations. One of them concerns the appearance of a negative charge on the carbon surface, when the latter is apparently neutral. Using first-principles density functional theory combined with molecular dynamics, we develop here several simulations on different systems in order to understand the reactivity of the carbon surface in low or ultra-high confinement. According to our calculations, there is high affinity of the carbon atom to the hydrogen ion in every situation, and to a lesser extent for the hydroxyl ion. The latter can only occur when the first hydrogen attack has been achieved. As a consequence, the functionalization of the carbon surface in the presence of an aqueous medium is activated by its protonation, then allowing the reactivity of the anion.

The modification of the inner nanopore wall by polymers is currently used to change the specific properties of the nanosystem. Among them, the polyethylene glycol (PEG) is the most used to prevent the fouling and ensure the wettability. However, its properties depend mainly on the chain structure that is very difficult to estimate inside this confined space. Combining experimental and simulation approaches, we provide an insight to the consequence of the PEG presence inside the nanopore on the nanopore properties. We show, in particular, that the cation type in the electrolyte, together with the type of electrolyte (water or urea), is at the origin of the ion transport modification in the nanopore.