Effects of hydrocarbon chain length and temperature on the self-assembly of cationic single-chain and Gemini surfactants and their interactions with bovine serum albumin

Abstract

Protein-surfactant interaction has been a subject of extensive studies over the past few decades due to its importance in manifold applications, such as food industry, drug delivery, skin and body care products, and cosmetics. Mild surfactants are often used to extract membrane proteins while preserving native structure and functional properties of protein, whereas the strong ionic surfactants are known to bind to oppositely charged protein molecules, resulting in denaturation of native protein and complete loss of protein activity. In general, the ionic surfactants bind strongly to protein through electrostatic attraction between surfactant headgroups and oppositely charged amino acids residues, and through hydrophobic interaction between surfactant hydrophobic tails and non-polar amino acids residues. Extensive studies on the interactions between ionic surfactants and protein have been reported. However, most of them focus on single-chain surfactants such as sodium dodecyl sulfate (SDS) or alkyltrimethylammonium bromide (C n TAB). In recent years, cationic gemini surfactant, a kind of surfactant consisting of two identical hydrophobic chains and two polar headgroups covalently linked by a spacer group, has stimulated the considerable interests due to its lower critical micelle concentration (CMC), stronger surface activity, better solubility, stronger hydrophobic microdomain, and so on. Thus, gemini surfactant is expected to exhibit quite different interaction behavior with protein from single-chain surfactant. This work has investigated the effect of hydrophobic chain length and temperature on the self-assembly of two series of cationic surfactants, gemini hexamethylene-1,6-bis(alkyldimethylammonium bromide) (C n C6C n Br2, n =10, 12, and 14) and single-chain alkyl trimethylammonium bromide (C n TAB, n =10, 12, 14), and their interactions with BSA using well-established ITC technique. For the surfactant self-assembly process, the micellization enthalpy change ( Δ H mic) values are more exothermic with the hydrophobic chain increasing. The free energy changes of micellization ( Δ G mic) mainly come from the micellization entropy changes ( Δ S mic). Temperature has a slight effect on the critical micelle concentration (CMC), but it has a significant effect on the Δ H mic. In the studied temperature range, the Δ H mic values are negative, whereas the Δ S mic values are positive, and the absolute values of T Δ S mic are larger than those of Δ H mic, proving the micellization process is mainly entropy-driven. With the temperature increasing, the contribution of enthalpy change to the micellization becomes larger, whereas the contribution of entropy change to the micellization becomes smaller. For the surfactant and bovine serum albumin (BSA) interaction process, at different surfactant concentration regions, the binding of the surfactants with BSA shows different interaction patterns. For most calorimetric curves of interactions, two endothermic and two exothermic processes are observed, and accompanied by two endothermic peaks. The first endothermic process is the dehydration of BSA upon the binding of the surfactant monomers. The first exothermic process involves the interaction of the surfactant monomers with surfactant molecules already bound on BSA molecule and the resultant formation of the micelle-like hydrophobic aggregates. The protein conformation change and the further dehydration of BSA molecules account for the second endothermic process. The following second exothermic process is the binding of surfactant monomers or micelles to BSA again leads to the formation of more micelle-like aggregates along the unfolded BSA molecules. The hydrophobic chain length remarkably affects the second endothermic process and the second exothermic process. This is because these two processes relate to the formation of the micelle-like aggregates along the BSA chain, whereas the micelle- like aggregates are easily formed at relatively high surfactant concentration range. The temperature has a marked effect on the protein/surfactant interaction in the first exothermic process and the second endothermic process. In particular, temperature strongly affects the appearance and amplitude of the second maximum endothermic peak, which can be explained by the effect of temperature on the protein conformation and the enthalpy change of micellization. In addition, gemini surfactants show much stronger binding ability with BSA as compared with single-chain surfactants due to their double hydrophobic chains and double charges.