Interaction of Linear Polyelectrolytes with Proteins: Role of Specific Charge-Charge Interaction and Ionic Strength.

Julia Bukala,Prabhusrinivas Yavvari,Marie Weinhart,Jacek Walkowiak,Matthias Ballauff

doi:10.3390/biom11091377

Julia Bukala, Prabhusrinivas Yavvari + Show 3 more

Open Access

https://doi.org/10.3390/biom11091377

Copy DOI

Abstract

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 (-SO3Na), cationic (-NH3Cl or -NHMe2Cl) or zwitterionic groups (-NMe2(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 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, ΔGb, as the function of the two decisive variables, temperature, T, and salt concentration, cs. The underlying model splits ΔGb 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.

Highlights

Linear polyelectrolytes may form well-defined complexes with proteins in dilute solution
The polyelectrolytes 1–4 were synthesized by post-modification of Poly(allyl glycidyl ether) (PAGE) (Mn = 12.1 kDa, Ð = 1.19) via thiol-ene reactions and purified by consecutive dialysis against salt solution and pure water
The opted post-modification strategy allowed the attainment of polyelectrolytes (Table S1) comprising the same number of around

Summary

Introduction

Linear polyelectrolytes may form well-defined complexes with proteins in dilute solution. Synthetic polyelectrolytes interacting with proteins have been the subject of intense studies [14,15,16,17,18,19]. The motivation for these investigations is two-fold: On the one hand, polymers are often appended to prevent the adsorption of proteins from aqueous solution [20]. Polyelectrolytes may form complex coacervates [16] with proteins that have found various applications, e.g., in food technology [17]

Methods

Results

Conclusion