Nonclassical Nucleation Pathways and Growth Kinetics of Protein Crystallization

• Applicant: Privatdozent Fajun Zhang, Ph.D.
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 364344939

• Final Report Year: 2022

Final Report Abstract

The research for this project focused on providing deeper understanding of nonclassical protein crystallization. To achieve this goal, we have first optimized the protein interactions and phase behavior in solution by fine-tuning the salt type, anions as well as composition. The optimized conditions for protein crystallization were further studied using real-time SAXS/SANS to characterize the structure and identify the role of MIP on crystal nucleation. Our results demonstrate that a metastable dense liquid phase may not contribute to the nucleation directly, instead, it may serve as a reservoir and be consumed via crystal growth. In the case of BLG-CdCl2 system, we find that the MIP is directly contributed to nucleation, furthermore, the MIPs are pre-ordered which further reduces the energy barrier of nucleation.

Publications

• Effective interaction, Global dynamics and cluster formation in protein solutions, PhD Dissertation. Universität Tübingen, Tübingen.
  Braun, M.K.
  
• Multivalent ions for tuning the phase behaviour of protein solutions. Institut für Angewandte Physik, PhD Dissertation. Universität Tübingen, Tübingen.
  Matsarskaia O.
  
• Reentrant Phase Behavior in Protein Solutions Induced by Multivalent Salts: Strong Effect of Anions Cl– Versus NO3–. The Journal of Physical Chemistry B, 122(50), 11978-11985.
  Braun, Michal K.; Sauter, Andrea; Matsarskaia, Olga; Wolf, Marcell; Roosen-Runge, Felix; Sztucki, Michael; Roth, Roland; Zhang, Fajun & Schreiber, Frank
  
• Tuning phase transitions of aqueous protein solutions by multivalent cations. Physical Chemistry Chemical Physics, 20(42), 27214-27225.
  Matsarskaia, Olga; Roosen-Runge, Felix; Lotze, Gudrun; Möller, Johannes; Mariani, Alessandro; Zhang, Fajun & Schreiber, Frank
  
• Following Protein Dynamics in Real Time during Crystallization. Crystal Growth & Design, 19(12), 7036-7045.
  Beck, Christian; Grimaldo, Marco; Roosen-Runge, Felix; Maier, Ralph; Matsarskaia, Olga; Braun, Michal; Sohmen, Benedikt; Czakkel, Orsolya; Schweins, Ralf; Zhang, Fajun; Seydel, Tilo & Schreiber, Frank
  
• Protein Crystallization in the Presence of a Metastable Liquid–Liquid Phase Separation. Crystal Growth & Design, 20(12), 7951-7962.
  Maier, Ralph; Zocher, Georg; Sauter, Andrea; Da Vela, Stefano; Matsarskaia, Olga; Schweins, Ralf; Sztucki, Michael; Zhang, Fajun; Stehle, Thilo & Schreiber, Frank
  
• Unification of lower and upper critical solution temperature phase behavior of globular protein solutions in the presence of multivalent cations. Soft Matter, 16(8), 2128-2134.
  Begam, Nafisa; Matsarskaia, Olga; Sztucki, Michael; Zhang, Fajun & Schreiber, Frank
  
• Human versus Bovine Serum Albumin: A Subtle Difference in Hydrophobicity Leads to Large Differences in Bulk and Interface Behavior. Crystal Growth & Design, 21(9), 5451-5459.
  Maier, Ralph; Fries, Madeleine R.; Buchholz, Cara; Zhang, Fajun & Schreiber, Frank
  
• Protein Crystallization from a Preordered Metastable Intermediate Phase Followed by Real-Time Small-Angle Neutron Scattering. Crystal Growth & Design, 21(12), 6971-6980.
  Maier, Ralph; Sohmen, Benedikt; Da Vela, Stefano; Matsarskaia, Olga; Beck, Christian; Schweins, Ralf; Seydel, Tilo; Zhang, Fajun & Schreiber, Frank
  
• Phase behavior and nonclassical crystallization of protein solutions with multivalent salts. Institut für Angewandte Physik, PhD Dissertation. Universität Tübingen, Tübingen.
  Maier, R. A.