Hyaluronan macromolecules in electrolyte solutions and their interactions with proteins

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28110%2F17%3A63517195" target="_blank" >RIV/70883521:28110/17:63517195 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Hyaluronan macromolecules in electrolyte solutions and their interactions with proteins

Popis výsledku v původním jazyce

Hyaluronan (HA) is a natural negatively charged polyelectrolyte contained in the connective-tissue extracellular matrix (ECM). It is a major component of proteoglycan, the essential material of ECM, but it has also numerous regulatory effects on the cellular processes. Hyaluronan is also a technologically valuable material widely used in the design of drug carriers, tissue substitutes and hydrophilic gels [1]. Several experimental studies reported the influence of inorganic ions dissolved in the solution on its macromolecular structure, especially the random-coil dimensions and the persistence length of the chain. They found a decrease of the random-coil size when the electrolyte concentration increases, generally attributed to the shielding of the carboxylate-groups repulsion. We study the effect of the electrolyte environment on the hyaluronan random coils using molecular-dynamics (MD) simulations. First, an oligosaccharide of 48 monosaccharide units is equilibrated within the NpT ensemble containing water and the given electrolyte in a specified concentration. Subsequently, random coils of kDa to MDa size are constructed by repeated connections of its randomly selected fragments from randomly chosen simulation frames. The glycosidic connections obey the statistics of dihedral angles occurring in the simulated oligosaccharide. The mean values of the radius of gyration (Rg) and the persistence length are evaluated based on large ensembles of generated random coils. Equal calculations were carried out for a neutral analog of HA containing glucose instead of glucuronic acid. The simulated HA random coils correspond well with the experimental values as regards the Rg and the scaling with the macromolecule length [2]. In addition, the random coils shrink rapidly when the salt concentration increases, as expected for polyelectrolytes [3]. However, a similar effect was observed also for the neutral analog indicating that the electrostatic repulsion is not the key factor determining the macromolecular shape. Indeed, due to the distance of the charged groups and the chain rigidity the electrostatic force is minor in comparison with the other non-covalent interactions. Hence, the influence of ions on the HA macromolecule is mediated mainly by the neutral regions of the polymer, especially the polar groups strongly interacting with the ions. As a perspective, we plan to compare the influence of different salts on HA and its neutral analog in order to understand the detailed interactions of ions with both charged and neutral polysaccharides and to uncover differences between different ions in a sense of a “Hofmeister-like” series. Simultaneously, MD models of both the polysaccharides interacting with hyaladherins (HA-binding proteins) are being studied in order to find the key regions of the interaction of the two charged macromolecules.

Název v anglickém jazyce

Hyaluronan macromolecules in electrolyte solutions and their interactions with proteins

Popis výsledku anglicky

Hyaluronan (HA) is a natural negatively charged polyelectrolyte contained in the connective-tissue extracellular matrix (ECM). It is a major component of proteoglycan, the essential material of ECM, but it has also numerous regulatory effects on the cellular processes. Hyaluronan is also a technologically valuable material widely used in the design of drug carriers, tissue substitutes and hydrophilic gels [1]. Several experimental studies reported the influence of inorganic ions dissolved in the solution on its macromolecular structure, especially the random-coil dimensions and the persistence length of the chain. They found a decrease of the random-coil size when the electrolyte concentration increases, generally attributed to the shielding of the carboxylate-groups repulsion. We study the effect of the electrolyte environment on the hyaluronan random coils using molecular-dynamics (MD) simulations. First, an oligosaccharide of 48 monosaccharide units is equilibrated within the NpT ensemble containing water and the given electrolyte in a specified concentration. Subsequently, random coils of kDa to MDa size are constructed by repeated connections of its randomly selected fragments from randomly chosen simulation frames. The glycosidic connections obey the statistics of dihedral angles occurring in the simulated oligosaccharide. The mean values of the radius of gyration (Rg) and the persistence length are evaluated based on large ensembles of generated random coils. Equal calculations were carried out for a neutral analog of HA containing glucose instead of glucuronic acid. The simulated HA random coils correspond well with the experimental values as regards the Rg and the scaling with the macromolecule length [2]. In addition, the random coils shrink rapidly when the salt concentration increases, as expected for polyelectrolytes [3]. However, a similar effect was observed also for the neutral analog indicating that the electrostatic repulsion is not the key factor determining the macromolecular shape. Indeed, due to the distance of the charged groups and the chain rigidity the electrostatic force is minor in comparison with the other non-covalent interactions. Hence, the influence of ions on the HA macromolecule is mediated mainly by the neutral regions of the polymer, especially the polar groups strongly interacting with the ions. As a perspective, we plan to compare the influence of different salts on HA and its neutral analog in order to understand the detailed interactions of ions with both charged and neutral polysaccharides and to uncover differences between different ions in a sense of a “Hofmeister-like” series. Simultaneously, MD models of both the polysaccharides interacting with hyaladherins (HA-binding proteins) are being studied in order to find the key regions of the interaction of the two charged macromolecules.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů