title: Concentration-dependent changes in apparent diffusion coefficients as indicator for colloidal stability of protein solutions.
abstract: The colloidal stability of a protein solution during downstream processing, formulation, and storage is a key issue for the biopharmaceutical production process. Thus, knowledge about colloidal solution characteristics, such as the tendency to form aggregates or high viscosity, at various processing conditions is of interest. This work correlates changes in the apparent diffusion coefficient as a parameter of protein interactions with observed protein aggregation and dynamic viscosity of the respective protein samples. For this purpose, the diffusion coefficient, the protein phase behavior, and the dynamic viscosity in various systems containing the model proteins α-lactalbumin, lysozyme, and glucose oxidase were studied. Each of these experiments revealed a wide range of variations in protein interactions depending on protein type, protein concentration, pH, and the NaCl concentration. All these variations showed to be mirrored by changes in the apparent diffusion coefficient in the respective samples. Whereas stable samples with relatively low viscosity showed an almost linear dependence, the deviation from the concentration-dependent linearity indicated both an increase in the sample viscosity and probability of protein aggregation. This deviation of the apparent diffusion coefficient from concentration-dependent linearity was independent of protein type and solution properties for this study. Thus, this single parameter shows the potential to act as a prognostic tool for colloidal stability of protein solutions.
authors.affiliation: Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Katharina Christin
authors.initials: KC
authors.lastname: Bauer
authors.affiliation: Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Göbel
authors.affiliation: Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Schwab
authors.affiliation: Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Schermeyer
authors.affiliation: Institute of Process Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany. Electronic address: juergen.hubbuch@kit.edu.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hubbuch
mesh_terms: D000818:Animals; D002417:Cattle; D002645:Chickens; D003102:Colloids / Q000737:chemistry* / Q000378:metabolism*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005949:Glucose Oxidase / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007768:Lactalbumin / Q000737:chemistry* / Q000378:metabolism*; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism*; D055550:Protein Stability; D012996:Solutions; D014783:Viscosity
chemical_list: D003102:Colloids; D012996:Solutions; D007768:Lactalbumin; D005949:Glucose Oxidase; D009113:Muramidase
keywords: Concentrated protein solutions; Dynamic light scattering; Dynamic viscosity; Protein aggregation; Protein interactions; Protein phase behavior; Protein phase diagrams