Interactions and Transport of Charged Species in Bulk and at Interfaces

July 4, 2016 to July 7, 2016
Location : CECAM-AT

Concentration-Induced Protein Association due to Patchy Attractions

Malin Zackrisson Oskolkova
Novo Nordisk A/S, Denmark

Coauthor(s) : Weimin Li [1], Björn Persson [2], Johan Bergenholtz [3], Mikael Lund [2]
[2 ]Division of Theoretical Chemistry, Lund University, Lund, Sweden [3] Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden


The self association of the protein lactoferrin is studied in solution using scattering techniques. Effective static structure factors are discovered to exhibit either a monotonic or non-monotonic dependence on protein concentration in the small wavevector limit depending on the salt concentration. The behavior correlates with a non-monotonic dependence of the second virial coefficient on salt concentration, such that a maximum appears in the structure factor at low protein concentration when the second virial coefficient is negative and close to a minimum. The results are interpreted in terms of an integral equation theory with explicit dimers due to Wertheim, which provides a consistent framework able to explain the behavior in terms of a monomer-dimer equilibrium that appears due to a highly directional patch attraction. Short attraction ranges preclude trimer formation, which explains why the protein system behaves as if subject to a concentration dependent isotropic protein-protein attraction. Superimposing an isotropic interaction, comprising screened Coulomb repulsion and van der Waals attraction, on the patch attraction allows for a semi-quantitative modeling of the complete transition pathway from monomers in the dilute limit to monomer-dimer systems at somewhat higher protein concentrations.


[1 ]B. A. Persson, M. Lund, J. Forsman, D. E. W. Chatterton,
and T. Åkesson, Biophys. Chem. 151 187 (2010)

[2] W. Li, B. A. Persson, M. Morin, M. A. Behrens, M. Lund,
and M. Z. Oskolkova, J. Phys. Chem. B 119 503 (2015)