A molecular approach to bioseparations: protein-protein and protein-salt interactions

R.A. Curtis, L. Lue

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Many bioprocess separations involve manipulating the solution conditions to selectively remove or concentrate a target protein. The selectivity is determined by the thermodynamics of the protein solution, which are governed, at the molecular level, by protein-protein interactions. Thus, to optimise these processes, one must understand the precise nature of these interactions, how they are affected by the control parameters (e.g., temperature, ionic strength, pH), and how they relate to the solution properties of interest (e.g., protein solubility, protein stability, crystal nucleation rates). Recently, studies of protein-protein interactions have been motivated by the discovery of a crystallisation window, which places bounds on the protein-protein attraction that is required for crystallisation to be possible. This review focuses on experimental and theoretical studies of protein-protein interactions and discusses the current caps in understanding these forces. The first models for these interactions had been based on DLVO theory, which has proven useful for understanding protein-protein interactions in dilute electrolyte solutions. However, DLVO theory does not include such important effects as anisotropic interactions, solvation forces, and specific ion effects. Various approaches have been developed to include these phenomena although they are still not well understood. One outstanding issue concerns specific ion effects, which play a crucial role in biological systems. An initial step in understanding these effects might be to first rationalize protein-salt interactions. (c) 2005 Elsevier Ltd. All fights reserved.
Original languageEnglish
Pages (from-to)907-923
Number of pages17
JournalChemical Engineering Science
Volume61
Issue number3
DOIs
Publication statusPublished - Feb 2006

Keywords

  • proteins
  • phase equilibria
  • crystallisation
  • colloidal phenomena
  • intermolecular interactions
  • molecular thermodynamics

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