Interaction of linear polyelectrolytes with proteins: Role of specific charge-charge interaction and ionic strength
Julia Bukala, Prabhusrinivas Yavvari, Jacek J. Walkowiak, Matthias Ballauff, Marie Weinhart – 2021
We present a thermodynamic study of the interaction of synthetic, linear polyelectrolytes with bo-vine serum albumin (BSA). All polyelectrolytes are based on poly(allyl glycidyl ether) which has been modified by polymer-analogous reaction with anionic (-SO3Na), cationic (-NH3Cl or -NHMe2Cl) or zwitterionic groups (-N(Me)2(CH2)3SO3). While the anionic polymer shows a very weak interaction, the zwitterionic polymer exhibits no interaction with BSA (pI = 4.7) under the applied pH = 7.4, ionic strength (I = 23-80 mM) and temperature conditions (T = 20-37 °C). A strong binding, however, was observed for the polycations bearing primary amino or tertiary di-methyl amino groups which could be analyzed in detail by isothermal titration calorimetry (ITC). The analysis was done using an expression which describes the free energy of binding Gb as the function of the two decisive variables, temperature T and salt concentration cs. The underlying model splits Gb into a term related to counterion release and a term related to water release. While the number of released counter ions is similar for both systems, the release of bound water is more important for the primary amine compared to the tertiary N,N-dimethyl amine presenting polymer. This finding is further traced back to a closer contact of the polymers’ protonated pri-mary amino groups in the complex with oppositely charged moieties of BSA as compared to the bulkier protonated tertiary amine groups. We thus present an investigation that quantifies both driving forces for electrostatic binding, namely counterion release and change of hydration, which contribute to a deeper understanding with direct impact on future advancements in the biomedical field.