Thermodynamics of the Coil ⇆ β-Sheet Transition in a Membrane Environment

Biologically important peptides such as the Alzheimer peptide Aβ(1–40) display a reversible random coil ⇆ β-structure transition at anionic membrane surfaces. In contrast to the well-studied random coil ⇆ α-helix transition of amphipathic peptides, there is a dearth on information on the thermodynamic and kinetic parameters of the random coil ⇆ β-structure transition. Here, we present a new method to quantitatively analyze the thermodynamic parameters of the membrane-induced β-structure formation. We have used the model peptide (KIGAKI)3 and eight analogues in which two adjacent amino acids were substituted by their d-enantiomers. The positions of the d,d pairs were shifted systematically along the three identical segments of the peptide chain. The β-structure content of the peptides was measured in solution and when bound to anionic lipid membranes with circular dichroism spectroscopy. The thermodynamic binding parameters were determined with isothermal titration calorimetry and the binding isotherms were analysed by combining a surface partition equilibrium with the Gouy–Chapman theory. The thermodynamic parameters were found to be linearly correlated with the extent of β-structure formation. β-Structure formation at the membrane surface is characterized by an enthalpy change of ΔHβ = − 0.23 kcal/mol per residue, an entropy change of ΔSβ = − 0.24 cal/mol K residue and a free energy change of ΔGβ = − 0.15 kcal/mol residue. An increase in temperature induces an unfolding of β-structure. The residual free energy of membrane-induced β-structure formation is close to that of membrane-induced α-helix formation.