title: Role of solvent properties of aqueous media in macromolecular crowding effects.
abstract: Analysis of the macromolecular crowding effects in polymer solutions show that the excluded volume effect is not the only factor affecting the behavior of biomolecules in a crowded environment. The observed inconsistencies are commonly explained by the so-called soft interactions, such as electrostatic, hydrophobic, and van der Waals interactions, between the crowding agent and the protein, in addition to the hard nonspecific steric interactions. We suggest that the changes in the solvent properties of aqueous media induced by the crowding agents may be the root of these "soft" interactions. To check this hypothesis, the solvatochromic comparison method was used to determine the solvent dipolarity/polarizability, hydrogen-bond donor acidity, and hydrogen-bond acceptor basicity of aqueous solutions of different polymers (dextran, poly(ethylene glycol), Ficoll, Ucon, and polyvinylpyrrolidone) with the polymer concentration up to 40% typically used as crowding agents. Polymer-induced changes in these features were found to be polymer type and concentration specific, and, in case of polyethylene glycol (PEG), molecular mass specific. Similarly sized polymers PEG and Ucon producing different changes in the solvent properties of water in their solutions induced morphologically different α-synuclein aggregates. It is shown that the crowding effects of some polymers on protein refolding and stability reported in the literature can be quantitatively described in terms of the established solvent features of the media in these polymers solutions. These results indicate that the crowding agents do induce changes in solvent properties of aqueous media in crowded environment. Therefore, these changes should be taken into account for crowding effect analysis.
authors.affiliation: a Cleveland Diagnostics , 3615 Superior Ave., Suite 4407B, Cleveland , OH 44114 , USA.
authors.forename: Luisa A
authors.initials: LA
authors.lastname: Ferreira
authors.affiliation: b Laboratory of Separation and Reaction Engineering, Department of Chemical Engineering , University of Porto , Dr. Roberto Frias St., 4200 465 Porto , Portugal.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Madeira
authors.affiliation: c Department of Molecular Medicine, Byrd Alzheimer's Research Institute, Morsani College of Medicine , University of South Florida , Tampa , FL 33612 , USA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.affiliation: d Department of Chemistry , Philipps University , Marburg , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Reichardt
authors.affiliation: b Laboratory of Separation and Reaction Engineering, Department of Chemical Engineering , University of Porto , Dr. Roberto Frias St., 4200 465 Porto , Portugal.|e Institute for Biological Instrumentation , Russian Academy of Sciences , 142290 Pushchino , Moscow Region , Russia.|f Faculty of Science, Biology Department , King Abdulaziz University , P.O. Box 80203, Jeddah 21589 , Kingdom of Saudi Arabia.|g Laboratory of Structural Dynamics, Stability and Folding of Proteins , Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: a Cleveland Diagnostics , 3615 Superior Ave., Suite 4407B, Cleveland , OH 44114 , USA.
authors.forename: Boris Y
authors.initials: BY
authors.lastname: Zaslavsky
mesh_terms: D006860:Hydrogen Bonding; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D011108:Polymers; D011506:Proteins; D012996:Solutions; D012997:Solvents; D014867:Water; D011092:Polyethylene Glycols
keywords: aqueous two-phase system; macromolecular crowding; partition; solvatochromic comparison; solvent properties