Secondary Nucleation of Aβ Revealed by Single-Molecule and Computational Approaches.

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.

Direct Defluorination and Amination of Polytetrafluoroethylene and Other Fluoropolymers by Lithium Alkylamides.

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.

Impact of Single-Walled Carbon Nanotube Functionalization on Ion and Water Molecule Transport at the Nanoscale.

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.

Translocation Processes of Pt(II)-Based Drugs through Human Breast Cancer Cell Membrane: Experiments.

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).

Modeling the Cellular Uptake of Functionalized Carbon Nanohorns Loaded with Cisplatin through a Breast Cancer Cell Membrane.

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.

Ultrasensitive Detection of Aβ42 Seeds in Cerebrospinal Fluid with a Nanopipette-Based Real-Time Fast Amyloid Seeding and Translocation Assay.

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.

Investigation of α-Synuclein and Amyloid-β(42)-E22Δ Oligomers Using SiN Nanopore Functionalized with L-Dopa.

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.

Nanovectorization of Ivermectin to avoid overdose of drugs.

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.

Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena.

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.

Detection of Amyloid-β Fibrils Using Track-Etched Nanopores: Effect of Geometry and Crowding.

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.

Impact of surface state on polyethylene glycol conformation confined inside a nanopore.

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.

Breaking the Controversy of the Electropolymerization of Pyrrole Mechanisms by the Effective Screening Medium Quantum Charged Model Interface.

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.

A potential solution to avoid overdose of mixed drugs in the event of Covid-19: Nanomedicine at the heart of the Covid-19 pandemic.

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.

From Behavior of Water on Hydrophobic Graphene Surfaces to Ultra-Confinement of Water in Carbon Nanotubes.

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.

Conformation of Polyethylene Glycol inside Confined Space: Simulation and Experimental Approaches.

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.

Theoretical study of ciprofloxacin antibiotic trapping on graphene or boron nitride oxide nanoflakes.

Reactions between the antibacterial fluoroquinolone agent ciprofloxacin (CIP) and organic hydrophilic nanoflakes (graphene oxide and boron nitride oxide) have been studied in aqueous medium using density functional theory (DFT), time-dependent density functional theory (TD-DFT), and molecular dynamics (MD) simulations. We found that CIP molecules in π-π electron donor-acceptor (EDA) reaction preserve their optical properties in water when adsorbed on hydrophilic nanoflakes. Moreover, MD calculations aimed at studying the diffusive translocation of CIP to lipid membrane showed that the choice of the hydrophilic nanovectors is primordial to stabilize the molecule on the cellular membrane and improve cytotoxic effects.

Polynucleotide differentiation using hybrid solid-state nanopore functionalizing with α-hemolysin.

We report results from full atomistic molecular dynamics simulations on the properties of biomimetic nanopores. This latter result was obtained through the direct insertion of an α-hemolysin protein inside a hydrophobic solid-state nanopore. Upon translocation of different DNA strands, we demonstrate here that the theoretical system presents the same discrimination properties as the experimental one obtained previously.

From Anodic Oxidation of Aliphatic α-Amino Acids to Polypeptides by Quantum Electrochemistry Approach: Beyond Miller-Urey Experiments.

For years, polypeptide formation has fascinated the scientific world because its understanding could lead to one of the possible explanations for the origin of life. Anodic oxidation of aliphatic α-amino acids in aqueous electrolytes can result either in their decomposition or in their polymerization into polypeptide. This behavior depends experimentally on both amino acid concentration and pH.

Ligand nanovectorization using graphene to target cellular death receptors of cancer cell.

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.

Influence of nanotube section on carboplatin confinement.

The confinement of anticancer carboplatin molecules (CBPT) in boron nitride nanotubes (BNNTs) with various sections was studied by means of density functional theory and molecular dynamic simulations. We show that the molecular insertion in BNNT is favored depending on the tube radius. The range of the energy adsorption varied from -1 eV to -2 eV depending on BNNT dimension.

Unexpected ionic transport behavior in hydrophobic and uncharged conical nanopores.

We investigated ionic transport behavior in the case of uncharged conical nanopores. To do so, we designed conical nanopores using atomic layer deposition of Al2O3/ZnO nanolaminates and then coated these with trimethylsilane. The experimental results are supported by molecular dynamics simulations.

The encapsulation of the gemcitabine anticancer drug into grapheme nest: a theoretical study.

The efficient transport of a drug molecule until its target cell constitutes a significant challenge for delivery processes. To achieve such objectives, solid nanocapsules that protect the immune system during the transport should be developed and controlled at the nanoscale level. From this point of view, nanostructures based on graphene sheets could present some promising properties due to their ultimate size and dimension.

Simulations of a Graphene Nanoflake as a Nanovector To Improve ZnPc Phototherapy Toxicity: From Vacuum to Cell Membrane.

We propose a new approach to improving photodynamic therapy (PDT) by transporting zinc phthalocyanine (ZnPc) in biological systems via a graphene nanoflake, to increase its targeting. Indeed, by means of time-dependent density functional theory simulations, we show that the ZnPc molecule in interaction with a graphene nanoflake preserves its optical properties not only in a vacuum but also in water. Moreover, molecular dynamic simulations demonstrate that the graphene nanoflake/ZnPc association, as a carrier, permits one to stabilize the ZnPc/graphene nanoflake system on the cellular membrane, which was not possible when using ZnPc alone.

Voltage-activated transport of ions through single-walled carbon nanotubes.

Ionic transport through single-walled carbon nanotubes (SWCNTs) is promising for many applications but remains both experimentally challenging and highly debated. Here we report ionic current measurements through microfluidic devices containing one or several SWCNTs of diameter of 1.2 to 2 nm unexpectedly showing a linear or a voltage-activated I-V dependence.

Controlling activation barrier by carbon nanotubes as nano-chemical reactors.

The oxidative addition of primary amine on a monocyclic phospholane was studied in confined conditions. This one-step chemical reaction has been investigated using the DFT technique to elucidate the role of confinement in carbon nanotubes on the reaction. Calculations were carried out by a progressive increase of the nanotube diameters from 10 Å to 15 Å in order to highlight the dependence of the reactivity on the nanotube diameter.