title: Single-molecule spectroscopy reveals polymer effects of disordered proteins in crowded environments.
abstract: Intrinsically disordered proteins (IDPs) are involved in a wide range of regulatory processes in the cell. Owing to their flexibility, their conformations are expected to be particularly sensitive to the crowded cellular environment. Here we use single-molecule Förster resonance energy transfer to quantify the effect of crowding as mimicked by commonly used biocompatible polymers. We observe a compaction of IDPs not only with increasing concentration, but also with increasing size of the crowding agents, at variance with the predictions from scaled-particle theory, the prevalent paradigm in the field. However, the observed behavior can be explained quantitatively if the polymeric nature of both the IDPs and the crowding molecules is taken into account explicitly. Our results suggest that excluded volume interactions between overlapping biopolymers and the resulting criticality of the system can be essential contributions to the physics governing the crowded cellular milieu.
authors.affiliation: Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soranno
authors.forename: Iwo
authors.initials: I
authors.lastname: Koenig
authors.forename: Madeleine B
authors.initials: MB
authors.lastname: Borgia
authors.forename: Hagen
authors.initials: H
authors.lastname: Hofmann
authors.forename: Franziska
authors.initials: F
authors.lastname: Zosel
authors.forename: Daniel
authors.initials: D
authors.lastname: Nettels
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schuler
mesh_terms: D000595:Amino Acid Sequence; D001704:Biopolymers / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*; D008970:Molecular Weight; D011485:Protein Binding; D012996:Solutions; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D001704:Biopolymers; D064267:Intrinsically Disordered Proteins; D046911:Macromolecular Substances; D012996:Solutions
keywords: Flory–Huggins theory; excluded volume screening; single-molecule FRET; unfolded state collapse