TY - JOUR

T1 - Interaction of linear polyelectrolytes with proteins

T2 - Role of specific charge–charge interaction and ionic strength

AU - Bukala, Julia

AU - Yavvari, Prabhusrinivas

AU - Walkowiak, Jacek J.

AU - Ballauff, Matthias

AU - Weinhart, Marie

N1 - Acknowledgments: M.B. is indebted to Rainer Haag for continuous support. The publication of this article was funded through the Open Access Publication Fund of Freie Universität Berlin. Funding: This research was funded by the Federal Ministry of Education and Research Germany (BMBF) [Grant number FKZ: 13N13523].

PY - 2021/9/17

Y1 - 2021/9/17

N2 - We present a thermodynamic study of the interaction of synthetic, linear polyelectrolytes with bovine serum albumin (BSA). All polyelectrolytes are based on poly(allyl glycidyl ether) which has been modified by polymer-analogous reaction with anionic (-SO3 Na), cationic (-NH3 Cl or-NHMe2 Cl) or zwitterionic groups (-NMe2 (CH2 )3 SO3 ). 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 dimethyl amino groups, which could be analysed 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 primary 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.

AB - We present a thermodynamic study of the interaction of synthetic, linear polyelectrolytes with bovine serum albumin (BSA). All polyelectrolytes are based on poly(allyl glycidyl ether) which has been modified by polymer-analogous reaction with anionic (-SO3 Na), cationic (-NH3 Cl or-NHMe2 Cl) or zwitterionic groups (-NMe2 (CH2 )3 SO3 ). 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 dimethyl amino groups, which could be analysed 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 primary 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.

KW - Complex formation

KW - Counterion release

KW - ITC

KW - Polycation

KW - Thermodynamic analysis

UR - http://www.scopus.com/inward/record.url?scp=85115099830&partnerID=8YFLogxK

U2 - 10.3390/biom11091377

DO - 10.3390/biom11091377

M3 - Article

AN - SCOPUS:85115099830

VL - 11

JO - Biomolecules

JF - Biomolecules

IS - 9

M1 - 1377

ER -