title: Strong Isotope Effects on Effective Interactions and Phase Behavior in Protein Solutions in the Presence of Multivalent Ions.
abstract: In this article, we have studied the influence of the isotopic composition of the solvent (H2O or D2O) on the effective interactions and the phase behavior of the globular protein bovine serum albumin in solution with two trivalent salts (LaCl3and YCl3). Protein solutions with both salts exhibit a reentrant condensation phase behavior. The condensed regime (regime II) in between two salt concentration boundaries (c* < cs< c**) is significantly broadened by replacing H2O with D2O. Within regime II, liquid-liquid phase separation (LLPS) occurs. The samples that undergo LLPS have a lower critical solution temperature (LCST). The value of LCST decreases significantly with increasing solvent fraction of D2O. The effective protein-protein interactions characterized by small-angle X-ray scattering demonstrate that although changing the solvent has negligible effects below c*, where the interactions are dominated by electrostatic repulsion, an enhanced effective attraction is observed in D2O above c*, consistent with the phase behavior observed. As the LCST-LLPS is an entropy-driven phase transition, the results of this study emphasize the role of entropy in solvent isotope effects.
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Michal K
authors.identifier: 0000-0002-9642-7492
authors.initials: MK
authors.lastname: Braun
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Marcell
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Matsarskaia
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Stefano
authors.initials: S
authors.lastname: Da Vela
authors.affiliation: Institut Laue-Langevin , 71 Avenue des Martyrs, 38000 Grenoble, France.
authors.forename: Felix
authors.initials: F
authors.lastname: Roosen-Runge
authors.affiliation: ESRF - The European Synchrotron , 71 Avenue des Martyrs, 38000 Grenoble, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Sztucki
authors.affiliation: Institut für Theoretische Physik, Universität Tübingen , Auf der Morgenstelle 14, 72076 Tübingen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Roth
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Fajun
authors.identifier: 0000-0001-7639-8594
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institut für Angewandte Physik, Universität Tübingen , Auf der Morgenstelle 10, 72076 Tübingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D002417:Cattle; D002712:Chlorides / Q000737:chemistry; D003903:Deuterium; D007811:Lanthanum / Q000737:chemistry*; D044367:Phase Transition; D055503:Protein Multimerization; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D044366:Transition Temperature; D014867:Water / Q000737:chemistry; D015019:Yttrium / Q000737:chemistry*
chemical_list: D002412:Cations; D002712:Chlorides; C028521:lanthanum chloride; D014867:Water; C064782:yttrium chloride; D012710:Serum Albumin, Bovine; D015019:Yttrium; D007811:Lanthanum; D003903:Deuterium