Self-assembly in patchy proteins: From transient networks to attractive glasses
July 31-August 4, 2017
Dynamic properties of crowded protein solutions are difficult to predict and control. This for example considerably limits our ability to create stable and injectable formulations of proteins or peptides at high concentrations. Another physiologically relevant case is presbyopia, or age-related farsightedness, where the pathological stiffening of the eye lens can be related to a liquid-solid transition of the protein mixtures inside the eye lens cells1. It is thus essential to achieve a quantitative understanding of the link between the molecular structure of the proteins and the interactions between them, and how these interactions influence the stability, dynamics and flow properties of the solutions as a function of their concentration. Here we show how we can use a combination of advanced characterization techniques1-4 such as neutron spin echo, small-angle scattering, 3D cross correlation light scattering and microrheology, combined with state-of-the-art computer simulations to assess and predict interparticle interactions and their impact on the dynamics and flow behavior of crowded protein solutions. We particularly point out the enormous influence of weak attractive interactions known to exist between many globular proteins, and demonstrate the dramatic effect of an interaction potential anisotropy such as attractive patches4 and shape anisotropy on the dynamic properties.
 G. Foffi, G. Savin, S. Bucciarelli, N. Dorsaz, G. Thurston, A. Stradner, P. Schurtenberger; "A Hard Sphere-Like Glass Transition in Eye Lens Alpha Crystallin Solutions"; Proc. Natl. Acad. Sci. U. S. A., 111, 16748-16753 (2014).
 F. Cardinaux, E. Zaccarelli, A. Stradner, S. Bucciarelli, B. Farago, S. Egelhaaf, F. Sciortino, P. Schurtenberger; "Cluster-driven dynamical arrest in concentrated lysozyme solutions" J. Phys. Chem. B, 115, 7227 (2011).
 S. Bucciarelli, L. Casal-Dujat, C. De Michele, F. Sciortino, J. Dhont, J. Bergenholtz, B. Farago, P. Schurtenberger, and A. Stradner; "Unusual Dynamics of Concentration Fluctuations in Solutions of Weakly Attractive Globular Proteins"; The Journal of Physical Chemistry Letters, 6, 4470-4474 (2015).
 S. Bucciarelli, J. S. Myung, B. Farago, S. Das, G. A. Viegenthart, O. Holderer, R. G. Winkler, P. Schurtenberger, G. Gompper, and A. Stradner; "Dramatic Influence of Attractions on Short-Time Protein Diffusion under Crowded Conditions"; Science Advances, 2, e1601432 (2016).
Anna Stradner, Jin Suk Myung, Tommy Garting, Felix Roosen-Runge, Peter Schurtenberger, Roland G. Winkler, and Gerhard Gompper, "Self-assembly in patchy proteins: From transient networks to attractive glasses" in "Association in Solution IV", Ulf Olsson, Lund University, Sweden Norman Wagner, University of Delaware, USA Anand Yethiraj, Memorial University of Newfoundland, Canada Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/assoc_solution_iv/19