Comicellization of polystyrene-block-poly(acrylic acid) with low-molar-mass surfactants

Tato bakalářská práce se zabývá studiem vlivu nízkomolekulárních iontových surfaktantů dodecylsulfátu sodného (SDS) a hexadecyltrimethylammonium bromidu (HTAB) na asociační chování blokového kopolymeru polystyren-b-polyakrylové kyseliny (PS-b-PAA) v alkalických vodných roztocích. Připravené polymerní nanočástice byly charakterizovány pomocí statického a dynamického rozptylu světla, transmisní elektronové mikroskopie a 1 H NMR spektroskopie. Bylo zjištěno, že oba surfaktanty interagují pouze s polyakrylátovými bloky a jejich přítomnost v systému vede ke zhoršení rozpustnosti kopolymeru, která se projevuje tvorbou velkých micelárních agregátů a srážením komplexu polymer-surfaktant.This B.Sc. thesis deals with the study of the effect of low-molar-mass ionic surfactants sodium dodecyl sulfate (SDS) and hexydecyltrimethylammonium bromide (HTAB) on association behavior of the block copolymer polystyrene-b-polyacrylic acid (PS-b-PAA) in alkaline aqueous solutions. Prepared polymeric nanoparticles were characterized by static and dynamic light scattering, transmission electron microscopy and 1 H NMR spectroscopy. It was found that both surfactants interact only with PAA blocks and their presence in the system leads to worsening of the copolymer solubility which manifests itself in the formation of large micellar aggregates and in precipitation of the copolymer-surfactant complexes.Department of Physical and Macromolecular ChemistryKatedra fyzikální a makromol. chemieFaculty of SciencePřírodovědecká fakult

Are You Tampering With My Data?

We propose a novel approach towards adversarial attacks on neural networks (NN), focusing on tampering the data used for training instead of generating attacks on trained models. Our network-agnostic method creates a backdoor during training which can be exploited at test time to force a neural network to exhibit abnormal behaviour. We demonstrate on two widely used datasets (CIFAR-10 and SVHN) that a universal modification of just one pixel per image for all the images of a class in the training set is enough to corrupt the training procedure of several state-of-the-art deep neural networks causing the networks to misclassify any images to which the modification is applied. Our aim is to bring to the attention of the machine learning community, the possibility that even learning-based methods that are personally trained on public datasets can be subject to attacks by a skillful adversary.Comment: 18 page

Stacked or folded? impact of chelate cooperativity on the self-assembly pathway to helical nanotubes from dinucleobase monomers

Self-assembled nanotubes exhibit impressive biological functions that have always inspired supramolecular scientists in their efforts to develop strategies to build such structures from small molecules through a bottom-up approach. One of these strategies employs molecules endowed with self-recognizing motifs at the edges, which can undergo either cyclization-stacking or folding-polymerization processes that lead to tubular architectures. Which of these self-assembly pathways is ultimately selected by these molecules is, however, often difficult to predict and even to evaluate experimentally. We show here a unique example of two structurally related molecules substituted with complementary nucleobases at the edges (i.e., G:C and A:U) for which the supramolecular pathway taken is determined by chelate cooperativity, that is, by their propensity to assemble in specific cyclic structures through Watson-Crick pairing. Because of chelate cooperativities that differ in several orders of magnitude, these molecules exhibit distinct supramolecular scenarios prior to their polymerization that generate self-assembled nanotubes with different internal monomer arrangements, either stacked or coiled, which lead at the same time to opposite helicities and chiroptical propertiesFunding from the European Research Council (ERC-Starting Grant 279548 PROGRAM-NANO) MCIN (RED2018- 102331-T, PID2020-116921GB-I00, and TED2021-132602BI00), the Italian Ministry of Education, University and Research (PRIN project prot. 2017A4XRCA_003), the Ministry of Education, Youth, and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/16_019/0000754, e-INFRA CZ (ID:90254)), the Swedish Research Council (2018- 4343), and the Swedish e-Science Research Centre (SeRC) is gratefully acknowledged. The authors also acknowledge the provision of supercomputer resources from the Swedish National Infrastructure for Computing (SNIC). F.A. is grateful to MCIN and Next Generation EU funding for a “Ramon-yCajal” fellowship (RyC-2021-031538-I). A.dJ. is grateful to EU funding from a MSCA-IEF action (897507-SuprAlloCat

Effects of lipid composition on membrane permeation

© 2018 The Royal Society of Chemistry. Passive permeation through lipid membranes is an essential process in biology. In vivo membranes typically consist of mixtures of lamellar and nonlamellar lipids. Lamellar lipids are characterized by their tendency to form lamellar sheet-like structures, which are predominant in nature. Nonlamellar lipids, when isolated, instead form more geometrically complex nonlamellar phases. While mixed lamellar/nonlamellar lipid membranes tend to adopt the ubiquitous lamellar bilayer structure, the presence of nonlamellar lipids is known to have profound effects on key membrane properties, such as internal distributions of stress and elastic properties, which in turn may alter related biological processes. This work focuses on one such process, i.e., permeation, by utilising atomistic molecular dynamics simulations in order to obtain transfer free energy profiles, diffusion profiles and permeation coefficients for a series of thirteen small molecules and drugs. Each permeant is tested on two bilayer membranes of different lipid composition, i.e., purely lamellar and mixed lamellar/nonlamellar. Our results indicate that the presence of nonlamellar lipids reduces permeation for smaller molecules (molecular weight 100). This work represents an advancement towards the development of more realistic in silico permeability assays, which may have a substantial future impact in the area of rational drug design

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from “pulling” coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives

Symposium Report The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

ABSTRACT This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b 5 . First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b 5 and 17a-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b 5 . The role of b 5 was also shown in vivo by selective hepatic knockout of b 5 from mice expressing CYP3A4 and CYP2D6; the lack of b 5 caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function

Comicellization of polystyrene-block-poly(acrylic acid) with low-molar-mass surfactants

This B.Sc. thesis deals with the study of the effect of low-molar-mass ionic surfactants sodium dodecyl sulfate (SDS) and hexydecyltrimethylammonium bromide (HTAB) on association behavior of the block copolymer polystyrene-b-polyacrylic acid (PS-b-PAA) in alkaline aqueous solutions. Prepared polymeric nanoparticles were characterized by static and dynamic light scattering, transmission electron microscopy and 1 H NMR spectroscopy. It was found that both surfactants interact only with PAA blocks and their presence in the system leads to worsening of the copolymer solubility which manifests itself in the formation of large micellar aggregates and in precipitation of the copolymer-surfactant complexes

Comicellization of polystyrene-block-poly(acrylic acid) with low-molar-mass surfactants

This B.Sc. thesis deals with the study of the effect of low-molar-mass ionic surfactants sodium dodecyl sulfate (SDS) and hexydecyltrimethylammonium bromide (HTAB) on association behavior of the block copolymer polystyrene-b-polyacrylic acid (PS-b-PAA) in alkaline aqueous solutions. Prepared polymeric nanoparticles were characterized by static and dynamic light scattering, transmission electron microscopy and 1 H NMR spectroscopy. It was found that both surfactants interact only with PAA blocks and their presence in the system leads to worsening of the copolymer solubility which manifests itself in the formation of large micellar aggregates and in precipitation of the copolymer-surfactant complexes

Influence of Membrane Phase on the Optical Properties of DPH

The fluorescent molecule diphenylhexatriene (DPH) has been often used in combination with fluorescence anisotropy measurements, yet little is known regarding the non-linear optical properties. In the current work, we focus on them and extend the application to fluorescence, while paying attention to the conformational versatility of DPH when it is embedded in different membrane phases. Extensive hybrid quantum mechanics/molecular mechanics calculations were performed to investigate the influence of the phase- and temperature-dependent lipid environment on the probe. Already, the transition dipole moments and one-photon absorption spectra obtained in the liquid ordered mixture of sphingomyelin (SM)-cholesterol (Chol) (2:1) differ largely from the ones calculated in the liquid disordered DOPC and solid gel DPPC membranes. Throughout the work, the molecular conformation in SM:Chol is found to differ from the other environments. The two-photon absorption spectra and the ones obtained by hyper-Rayleigh scattering depend strongly on the environment. Finally, a stringent comparison of the fluorescence anisotropy decay and the fluorescence lifetime confirm the use of DPH to gain information upon the surrounding lipids and lipid phases. DPH might thus open the possibility to detect and analyze different biological environments based on its absorption and emission properties