Polycationic Chains Research Articles

Spectroscopic and solution properties characterization of quaternary ammonium ion containing polycations complexed with fluorescent rhodamine sulfonic acid dyes

Based on the growing range of applications for polycations in research and commercial materials, a continuing need exists to advance the fundamental knowledge and understanding of this class of materials. Spectroscopic and solution properties characterizations of noncovalently labeled, fluorescent Alexa Fluor® dye complexes of two commercial polycations, poly(2-(trimethylamino) ethyl methacrylate) monocation and poly[bis[2-chloroethyl] ether-alt-1,3-bis[3-(dimethylamino) propyl] urea] dication are reported to help address this need. A variety of fluorescence spectroscopic methods are used with a special emphasis on fluorescence correlation spectroscopy (FCS) which is applied to characterize the Stokes radius (RS) and equilibrium dissociation constants (Kd) of dye-polycation complexes at nanomolar dye concentrations. Resulting RS values indicate dye binding to individual polycation chains. Measured Kd values in the sub-micromolar range are consistent with strong dye binding. Increasing solution ionic strength with sodium chloride addition inhibits dye binding and decreases the RS of dye-polycation complexes due to size collapse of polycation chains. The complexes differ in their solution stability to ionic strength changes suggesting that both electrostatic and hydrophobic binding interactions influence dye binding. This study establishes the viability of noncovalent dye-polycation complexation in concert with FCS characterization as a general approach for investigating the properties of quaternary ammonium ion containing polycations in aqueous solution.

Functional derivatives of chitosan, soluble in neutral medium as drugs and genetic material carrier: preparation and properties

Method of chitosan modification, providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. Presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA — polyplexes, stable under conditions close to physiological ones has been demonstrated. It was shown the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery system. The 2-stage method of chitosan modification providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. The presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA, polyplexes stable under conditions close to physiological ones has been demonstrated. It is shown that the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery systems.

Cationic homopolypeptides: A versatile tool to design multifunctional antimicrobial nanocoatings

Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.

Giant Iontronic Flexoelectricity in Soft Hydrogels Induced by Tunable Biomimetic Ion Polarization.

Flexoelectricity features the strain gradient-induced mechanoelectric conversion using materials not limited by their crystalline symmetry, but state-of-the-art flexoelectric materials exhibit very small flexoelectric coefficients and are too brittle to withstand large deformations. Here, inspired by the ion polarization in living organisms, this paper reports the giant iontronic flexoelectricity of soft hydrogels where the ion polarization is attributed to the different transfer rates of cations and anions under bending deformations. The flexoelectricity is found to be easily regulated by the types of anion-cation pairs and polymer networks in the hydrogel. A polyacrylamide hydrogel with 1m NaCl achieves a record-high flexoelectric coefficient of ≈1160 µC m-1, which can even be improved to ≈2340 µC m-1 by synergizing with the effects of ion pairs and extra polycation chains. Furthermore, the hydrogel as flexoelectric materials can withstand larger bending deformations to obtain higher polarization charges owing to its intrinsic low modulus and high elasticity. A soft flexoelectric sensor is then demonstrated for object recognition by robotic hands. The findings greatly broaden the flexoelectricity to soft, biomimetic, and biocompatible materials and applications.

Programming viscoelastic properties in a complexation gel composite by utilizing entropy-driven topologically frustrated dynamical state

Hydrogel composites in an aqueous media with viscoelastic properties and elastic modulus that can be precisely tailored are desirable to mimic many biological tissues ranging from mucus, vitreous humor, and nucleus pulposus as well as build up biosensors. Without altering the chemistry, tuning the physical interactions and structures to govern the viscoelastic properties of the hydrogels is indispensable for their applications but quite limited. Here we design a complexation gel composite and utilize the physical principle of topologically frustrated dynamical state to tune the correlated structures between the guest polycation chains and negatively charged host gels. We precisely quantify the mesh size of the host gel and guest chain size. By designing various topologically correlated structures, a viscoelastic moduli map can be built up, ranging from tough to ultrasoft, and from elastic-like with low damping properties to viscous-like with high damping properties. We also tune the swelling ratio by using entropy effect and discover an Entropy-driven Topologically Isovolumetric Point. Our findings provide essential physics to understand the relationship between entropy-driven correlated structures and their viscoelastic properties of the complexation hydrogel composites and will have diverse applications in tissue engineering and soft biomaterials.

A Molecular Thermodynamic Model of Coacervation in Solutions of Polycations and Oppositely Charged Micelles.

To guide the rational design of personal care formulations, we formulate a molecular thermodynamic model that predicts coacervation from cationic polymers and mixed micelles containing neutral and anionic surfactants and added salt. These coacervates, which form as a result of dilution of conditioning shampoos during use, deposit conditioning agents and other actives to the scalp or skin and also provide lubrication benefits. Our model accounts for mixing entropy, hydrophobic interactions of polycation with water, free energies of bindings of oppositely charged groups to micelles and polycations, and electrostatic interactions that capture connectivity of charged groups on the polycation chain and the micelle. The model outputs are the compositions of surfactants, polycation, salt, and water in the coacervate and in its coexisting dilute phase, along with the binding fractions and coacervate volume fraction. We study the effects of overall composition (of surfactant, polycation, and added salt), charge fractions on micelles and polycations, and binding free energies on the phase diagram of coacervates. Then, we perform coacervation experiments for three systems: sodium dodecyl sulfate (SDS)-JR30M, sodium methyl cocoyl taurate (Taurate)-JR30M, and sodium lauryl alaninate (Alaninate)-JR30M, where JR30M is a cationic derivative of hydroxyethylcellulose (cat-HEC), and rationalize their coacervation data using our model. For comparison with experiment, we also develop a parametrization scheme to obtain the requisite binding energies and Flory-Huggins χ parameter. We find that our model predictions agree reasonably well with the experimental data, and that the sulfate-free surfactants of Taurate and Alaninate display much larger 2-phase regions compared to SDS with JR30M.

Abatement of some commercial fungicide content from model dispersions by a new thiourea-graft-polyethyleneimine derivative

A new derivative of polyethyleneimine (PEI) with 9% degree of substitution of its primary and secondary amino groups with thiourea moieties (TU9-PEI) has been synthesized and investigated as flocculant in model suspensions of commercial fungicide formulations Dithane M45, Melody Compact 49 WG, Cabrio®Top, and their mixtures. The structure of TU9-PEI, obtained by an aqueous one-pot strategy involving formaldehyde mediated coupling of PEI and TU, was confirmed by FTIR and 1H NMR spectroscopy as well as the streaming potential measurements. The settling time, polymer dose, and fungicide type and concentration were the parameters used for assessing the flocculation ability of the new polycation sample. The UV-Vis spectroscopy measurements revealed a good removal efficiency of TU9-PEI for all of the fungicides investigated, between 88 and 94%. Slightly higher removal percent was found for greater fungicide concentrations. The charge neutralization was indicated by zeta potential measurements (values close to zero recorded at the optimum polymer dose) as the main mechanism which contributed to the Dithane and Cabrio®Top particle removal and a combined effect of the TU9-PEI/fungicide particle electrostatic attractions and hydrogen bonds between both the amine and thiourea groups of the polycation chains and the hydroxyl ones on the copper oxychloride particles (negative values) in case of the Melody Compact 49 WG particle separation. Particle size and surface morphology analysis data gave supplementary evidences regarding the TU9-PEI ability to separate the fungicides investigated from simulated wastewater.

Ab Initio Study of H-Bond Dynamics in Three-Component Crystals Comprising (DABCOH+ )n Polycationic Chains.

In this work, the dynamic character of hydrogen-bond (H-bond) networks in two three-component crystals comprising polycationic chains was described. The first studied system was 1,4-diazabicyclo[2.2.2]octan-1-ium (DABCOH+ ) sulfamate monohydrate, known for its large negative linear compressibility. The second analyzed material was the newly obtained polar salt co-crystal: 1,4-diazabicyclo[2.2.2]octan-1-ium sulfamate urea. X-ray diffraction measurements enabled us to study the H-bond systems in both crystals using the graph set analysis. Obtained structures served as the initial models for Born-Oppenheimer molecular dynamics computations. A detailed study of intermolecular interactions and power spectra was conducted. The analysis of time and space correlations between the changes in H-bonds enabled the detection of proton transfer occurring in both systems at 300 K. Further study of those dynamic phenomena was done using the Energy Decomposition Analysis for selected trajectory fragments. Our work should improve the understanding of dielectric and ferroelectric properties of hybrid organic-inorganic materials.

Self-Activated Cascade Biocatalysis of Glucose Oxidase-Polycation-Iron Nanoconjugates Augments Cancer Immunotherapy.

Biocatalytic therapy by reactive-oxygen-species-generating enzymes not only kills cancer cells directly but also stimulates an anticancer immune response and inverses the immunosuppressive microenvironment of a variety of solid tumors, which is potentially beneficial to overcoming the limitations of cancer immunotherapy. Herein, we report the in situ growth of polycation chains from glucose oxidase to generate glucose oxidase-polycation conjugates, which can be used as a template for the in situ reduction of ferrous ions into iron nanoparticles to yield glucose oxidase-polycation-iron nanoconjugates. The nanoconjugates exhibit enhanced cellular uptake and cancer retention as well as self-activated cascade biocatalysis that consumes glucose and generates highly toxic hydroxyl radicals, leading to enhanced starvation-like and chemodynamic cancer therapy. The cancer treatment with the nanoconjugates efficiently triggers the program of immunogenic cell death for enhanced immune checkpoint blockade therapy. The synergy of self-activated cascade biocatalysis and immune checkpoint blockade not only eradicates primary cancers but also inhibits the progression of distant cancers, which leads to the abscopal effect on cancers. Our findings provide a method for the in situ synthesis of self-activated cascade nano-biocatalysts for cascade biocatalysis-enhanced immunotherapy of cancer.

Label-free electrical monitoring of nucleic acid amplification with integrated hydrogel ionic diodes.

We demonstrate here for the first time the utility of a monolithically integrated hydrogel ionic diode for label-free quantitative DNA detection and real-time monitoring of nucleic acid amplification. The hydrogel ionic diode presented herein, unlike nanomaterial-based field-effect biosensors, features high cost-effectiveness and convenient fabrication. This is realized by patterning a micrometer-sized heterojunction consisting of adjacent segments of polycationic and polyanionic hydrogels on a microfluidic chip through simple photocuring steps. The integrated diode rectifies ionic currents being sensitive to the charge of DNA adsorbed onto the polycationic chains through electrostatic associations. Based on the mechanism, we show that the ionic biosensor can electrically quantify DNA in a dynamic range relevant to typical nucleic acid amplification assays. Utilizing the device, we demonstrate the evaluation of a PCR assay amplifying a 500-bp DNA fragment of E. coli, an infection-causing pathogen, and real-time in situ monitoring of an isothermal assay amplifying E. coli whole genome. We anticipate that the device could potentially pave the way for miniaturized optics-free platforms for quantifying nucleic acid amplification at point-of-care.

Simultaneous electrokinetic energy conversion and organic molecular sieving by two-dimensional confined nanochannels

With the development of nanofabrication and nanomaterials, electrokinetic nanofluidic energy conversion has been studied in nanometre-scale, even sub-1-nm channels, which can sieve organic molecules. However, achieving simultaneous nanofluidic energy conversion and organic molecular sieving still remains a challenge. In this work, functional MXene-based membranes were prepared for simultaneous electrokinetic energy conversion and organic molecular sieving. The surface charges of MXene-based membranes were successfully transferred from negative to positive by functionalizing poly (diallyldimethylammonium chloride) (PDDA) polycation chain. The positively charged PDDA-MXene (PMXene) composite membranes displayed good rejection (greater than 99 %) for positively charged methylene blue (MB) molecules. The streaming currents through PMXene and MXene membranes were opposite, indicating the successful modification of the surface charge in the nanochannels of the membranes. In addition, the output current improved around four times from ∼ 95 nA (50 kPa) to ∼ 380 nA (150 kPa) through the PMXene membranes. The flux and rejection of the membranes can also be enhanced by tuning the applied pressure and the thickness of the membranes. Given the superior selective transport of ions and molecules, functional MXene-based membranes can offer many exciting opportunities for self-powered and energy recovery systems during the separation process.

Cover Feature: Syntheses and Structures of Protonated Acetylenedicarboxylic Acid (Eur. J. Inorg. Chem. 6/2022)

The Cover Feature shows diprotonated (top left) and monoprotonated acetylenedicarboxylic acid (bottom right), which were prepared in the binary superacidic systems HF/MF5 (M = As, Sb). The focus is on the hydrogen bond of the monoprotonated species, which is better described as twofold hemiprotonated. The structure is composed of acetylenedicarboxylic acid moieties connected via strong hydrogen bonds to polycationic chains. The tug-of-war represents this special situation with the indeterminate position of the proton between the two equally basic oxygen atoms. Cover design by Christoph Jessen. More information can be found in the Research Article by C. Jessen and A. J. Kornath.

Ion-Specific and Solvent Effects on PDADMA–PSS Complexation and Multilayer Formation

Among various parameters that influence the formation of polyelectrolyte complexes and multilayers, special emphasis should be placed on ion-specific and solvent effects. In our study, we systematically examined the above-mentioned effects on poly(diallyldimethylammonium chloride) (PDADMACl)-sodium poly(4-styrenesulfonate) (NaPSS) complexation in solution and at the surface by means of dynamic light scattering, ellipsometry and atomic force microscopy measurements. As solvents, we used water and water/ethanol mixture. The obtained results confirm the importance of ion-specific and solvent effects on complexes prepared in solution, as well as on multilayers built up on a silica surface. The experiments in mixed solvent solution showed that at a higher ethanol mole fraction, the decrease in monomer titrant to titrand ratio, at which the increase in the size of complexes is observed, takes place. The difference between chloride and bromide ions was more pronounced at a higher mole fraction of ethanol and in the case of positive complex formation, suggesting that the larger amount of bromide ions could be condensed to the polycation chain. These findings are in accordance with the results we obtained for polyelectrolyte multilayers and could be helpful for designing polyelectrolyte multilayers with tuned properties needed for various applications, primarily in the field of biomedicine.

Polycation-Anionic Lipid Membrane Interactions.

Natural or synthetic polycations are used as biocides or as drug/gene carriers. Understanding the interactions between these macromolecules and cell membranes at the molecular level is therefore of great importance for the design of effective polymer biocides or biocompatible polycation-based delivery systems. Until now, details of the processes at the interface between polycations and biological systems have not been fully recognized. In this study, we consider the effect of strong polycations with quaternary ammonium groups on the properties of anionic lipid membranes that we use as a model system for protein-free cell membranes. For this purpose, we employed experimental measurements and atomic-scale molecular dynamics (MD) simulations. MD simulations reveal that the polycations are strongly hydrated in the aqueous phase and do not lose the water shell after adsorption at the bilayer surface. As a result of strong hydration, the polymer chains reside at the phospholipid headgroup and do not penetrate to the acyl chain region. The polycation adsorption involves the formation of anionic lipid-rich domains, and the density of anionic lipids in these domains depends on the length of the polycation chain. We observed the accumulation of anionic lipids only in the leaflet interacting with the polymer, which leads to the formation of compositionally asymmetric domains. Asymmetric adsorption of the polycation on only one leaflet of the anionic membrane strongly affects the membrane properties in the polycation–membrane contact areas: (i) anionic lipid accumulates in the region near the adsorbed polymer, (ii) acyl chain ordering and lipid packing are reduced, which results in a decrease in the thickness of the bilayer, and (iii) polycation–anionic membrane interactions are strongly influenced by the presence and concentration of salt. Our results provide an atomic-scale description of the interactions of polycations with anionic lipid bilayers and are fully supported by the experimental data. The outcomes are important for understanding the correlation of the structure of polycations with their activity on biomembranes.

Microphase separation and aggregate self-assembly in brushes of oppositely charged polyelectrolytes triggered by ion pairing.

This work applies a molecular theory to study the formation of lateral self-assembled aggregates in mixed brushes composed of polyanion and polycation chains. In order to overcome the well-known limitations of mean-field electrostatics to capture polyelectrolyte complexation, the formation of ion pairs between anionic and cationic groups in the polyelectrolytes is explicitly modeled in our theory as an association reaction. This feature is essential to capture the microphase separation of the mixed brush and the formation of lateral aggregates triggered by polyelectrolyte complexation. The effects of solution pH and ionic strength, surface coverage, and chain length on the morphology of the mixed brush are systematically explored. It is shown that increasing salt concentration leads to the rupture of polyelectrolyte complexes and the stabilization of the homogeneous, non-aggregated brush, providing that the formation of ion pairs between the polyelectrolytes and the salt ions in solution is explicitly accounted for by the theory. The inclusion of ion-pairing association reactions between oppositely charged polyelectrolytes within a mean-field description of electrostatics emerges from this work as a useful and simple theoretical approach to capture the formation of polyelectrolyte complexes and their responsiveness to solution ionic strength and pH.

Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening.

Messenger RNA (mRNA) shows high therapeutic potential, though effective delivery systems are still needed for boosting its application. Nanocarriers loading mRNA via polyion complexation with block catiomers into core-shell micellar structures are promising systems for enhancing mRNA delivery. Engineering the interaction between mRNA and catiomers through polymer design can promote the development of mRNA-loaded micelles (mRNA/m) with increased delivery efficiency. Particularly, the polycation chain rigidity may critically affect the mRNA-catiomer interplay to yield potent nanocarriers, yet its effect remains unknown. Herein, the influence of polycation stiffness on the performance of mRNA/m by developing block complementary catiomers having polycation segments with different flexibility, that is, poly(ethylene glycol)-poly(glycidylbutylamine) (PEG-PGBA) and PEG-poly(L-lysine) (PEG-PLL) is studied. PEG-PGBA allows more than 50-fold stronger binding to mRNA than the relatively more rigid PEG-PLL, resulting in mRNA/m with enhanced protection against enzymatic attack and polyanions. mRNA/m from PEG-PGBA significantly enhances mRNA in vivo bioavailability and increased protein translation, indicating the importance of controlling polycation flexibility for forming stable polyion complexes with mRNA toward improved delivery.

Molecular-Level Insight into the Interactions of DNA/Polycation Complexes with Model Cell Membranes.

The interactions of DNA/polycation complexes (polyplexes) with cell membranes are crucial for understanding the molecular mechanisms behind polycation-mediated delivery of nucleic acid therapeutics into the target cells. In this study, we employed both biased and unbiased atomic-scale computer simulations to get an insight into such interactions. To this end, we considered complexes of DNA with linear polyethylenimine (PEI) with various polycation contents, ranging from an almost fully neutralized DNA to a highly overcharged polyplex. Our findings clearly show that the free energy gradually increases when a polyplex approaches the surface of a zwitterionic (neutral) phospholipid membrane from bulk water, implying the lack of attractive polyplex/membrane interactions. Remarkably, overcharging of DNA molecules by polycations enhances the repulsion between the polyplex and the zwitterionic lipid membrane. The observed repulsion is most likely driven by the dehydration of a polyplex upon its partitioning into the zwitterionic lipid membrane as well as by the loss of conformational entropy of PEI chains. We also demonstrate that cationic polymer chains are able to protect DNA from the dehydration as well as from contacts with lipid molecules. Interestingly, the absence of local minima in the free energy profiles does not exclude transient weak adsorption of a polyplex on the zwitterionic membrane surface. We show that such spontaneous adsorption can indeed be initiated by the interactions of loose polycation chains of the polyplex with polar head groups of lipids. Overall, our computational findings contribute considerably to the understanding of the initial stages in polycation-mediated DNA transfection. In particular, we demonstrate that a zwitterionic lipid bilayer represents an energetic barrier for polyplexes, so that a proper model of the cell membrane should account for the anionic surface charge of the membrane (e.g., due to the presence of proteoglycans).

Surfaces that Adhesively Discriminate Breast Epithelial Cell Lines and Lymphocytes in Buffer and Human Breast Milk.

We report new surface coatings that adhesively distinguish three breast epithelial cell lines (MCF-10A, MCF-7, and TMX2-28) when cell suspensions in buffer or breast milk are flowed over the coatings. We also report the selective capture of epithelial cells and rejection of Jurkat lymphocytes, with average selectivities exceeding 60 and captured cell purities often exceeding >99%. The surfaces achieve the dual goals of selective cell capture and resistance to fouling by proteins and other components of breast milk. The coatings do not rely on antibody targeting of cell surface markers but instead contain polycation chains embedded within a layer of end-tethered poly(ethylene glycol) (PEG) chains. The PEG, somewhat shielding the polycations, prevents surface fouling by proteins, nondesired cells, and other milk components, while the polycations produce electrostatic attractions that are heterogeneous on nanoscopic length scales. These electrostatic heterogeneities on the engineered coating, shown to produce curvature-selective particle capture in other studies, produce cell selectivity here. The ability of the engineered surfaces to discriminate these cell lines via an electrostatic driving force is remarkable, as the cells are of very similar surface charge as evidenced by their nearly identical ζ-potentials. The current surfaces, which likely distinguish cells based on their electrostatic surface landscape combined with other factors, adhesively distinguish cell lines that may differ only slightly in their expression of a surface marker, or cancer cells that minimally express EpCAM but which have different distributions of electrostatic charge on their surfaces. These surfaces are among the first to be documented for the compatibility of a polymer brush with human breast milk and may find use in technologies that capture cells from human breast milk or other complex fluids for cancer risk assessment.

Competitive Reactions in Three-Component System Cationic Colloid–Anionic Liposome–Protein

The formation of complexes of anionic liposomes (50 nm) and polymer microspheres with grafted polycationic chains with a diameter of 240 nm (spherical polycationic brushes) in a physiological solution at a NaCl concentration of 0.15 mol/L is investigated. Liposomes are quantitatively adsorbed on the surface of brushes; every brush can bind up to 24 intact liposomes. The saturated brush–liposome complex is able to additionally bind negatively charged protein albumin; the excess of protein does not displace liposomes from the complex with brushes. The obtained results are important for understanding the mechanism of formation and functioning of electrostatic multiliposomal containers in biological media containing a high amount of protein.

Protonation of β-lactoglobulin in the presence of strong polyelectrolyte chains: a study using Monte Carlo simulation

In this work, the molecular interaction between the protein β-lactoglobulin and strong polyelectrolyte chains was studied using Monte Carlo simulations. Different coarse-grained models were used to represent the system components. Both net charge and protonation of the isolated dimeric protein were analyzed as a function of pH. The acid-base equilibrium of each titratable group was distinctively modified by the presence of polyanion or polycation chains. The complexation on the wrong side of pI was more evident with the polycation than with the polyanion. It was mainly due to a charge regulation mechanism, where the reversion in net charge of the protein was more pronounced at the left of isoelectric point of the protein. The glutamic and aspartic groups play a key role in this charge reversion. Both polyanion and polycation were spatially adsorbed in different region on the protein surface, suggesting the importance of the surface charge distribution of the protein.