Frank Laboratory of Neutron Physics

Joint Laboratory Seminar

Leader – Shvetsov V.N.

Date and Time: Friday, 20 September 2019, at 11:00 AM

Venue: Conference hall (3rd floor), Frank Laboratory of Neutron Physics

Seminar topic: «Using Scattering to Understand Protein Behavior: Aggregation, Crystallization, Diffusion, and Adsorption»

Speaker: Frank Schreiber (Tuebingen University, Tuebingen, Germany)

Abstract:

We discuss concepts for controlling and understanding protein aggregation pathways and the branching between them in aqueous solution by addition of multivalent ions. This route for the tailoring of the interaction potential is exploited for controlling a) crystallization, b) gelation and amorphous aggregation, as well as c) smaller aggregate formation including their dynamics and kinetics. We also discuss the connection to and the role of interfaces in this context. Furthermore, we explain how scattering techniques can be employed to characterize these complex systems.
First, we present a real-time study of protein crystallization induced by multivalent ions using small-angle scattering and optical microscopy. Based on the crystallization kinetics, we propose a multistep mechanism. In the first step, an intermediate phase is formed, followed by the nucleation of crystals within the intermediate phase. During this period, the number of crystals increases with time, but the crystal growth is slowed down by the surrounding dense intermediate phase due to the low mobility. In the next step, the intermediate phase is consumed by nucleation and slow growth, and the crystals are exposed to the dilute phase. In this stage, the number of crystals becomes nearly constant, whereas the crystals grow rapidly due to access to the free protein molecules in the dilute phase.
Second, we present complementary investigations of the dynamics of these systems using quasi-elastic neutron scattering, showing a remarkably universal behaviour of the effective diffusion as a function of concentration and salt under suitable conditions. We also explore the dynamical behavior during phase transformation, such as cluster formation and crystallization. Third, we show how these concepts can be transferred to protein-interface interactions, and how adsorption behavior can be manipulated by multivalent charges. Using neutron reflectometry, we try to connect the interface and the bulk behavior, including reentrant adsorption and anomalous interface behavior upon approaching bulk phase boundaries.