Thermodynamic and structural characterization of zwitterionic micelles of the membrane protein solubilizing amidosulfobetaine surfactants ASB-14 and ASB-16

Surface tension and isothermal titration calorimetry (ITC) were used to determine the critical micelle concentration (cmc) of the zwitterionic amidosulfobetaine Surfactants ASB-14 and ASB-16 (linear-alkylamidopropyldimethylammoniopropanosulfonates) at 25 °C. The cmc and the heat of micellization were determined from 15 to 75 °C by ITC for both Surfactants. The increase in temperature caused significant changes in the enthalpy and in the entropy of micellization, with small changes in the standard Gibbs energy (ΔG(mic)), which is consistent to an enthalpy−entropy compensation with a compensatory temperature of 311 K (ASB-14) and 314 K (ASB-16). In the studied temperature range, the heat capacity of micellization (ΔC(p)(mic)) was essentially constant. The experimental ΔC(p)(mic) was lower than that expected if only hydrophobic interactions were considered, suggesting that polar interactions at the head groups are of significant importance in the thermodynamics of micelle formation by these Surfactants. Indeed, a NMR NOESY spectrum showed NOEs that are improbable to occur within the same monomer, resulting from interactions at the polar head groups involving more than one monomer. The ITC and NMR results indicate a tilt in the polar headgroup favoring the polar interactions. We have also observed COSY correlations typical of dipolar interactions that could be recovered with the partial alignment of the molecule in solution, which results in an anisotropic tumbling. The anisotropy suggested an ellipsoidal shape of the micelles, which results in a positive magnetic susceptibility, and ultimately in orientation induced by the magnetic field. Such an ellipsoidal shape was confirmed from results obtained by SAXS experiments that revealed aggregation numbers of 108 and 168 for ASB-14 and ASB-16 micelles, respectively. This study characterizes an interesting micelle system that can be used in the study of membrane proteins by solution NMR spectroscopy.