Domain formation induced by lipid-ion and lipid-peptide interactions

Abstract

High sensitivity titration calorimetry was performed for metal ions such as calcium and lanthanum and for different types of Alzheimer peptides. Ca²⁺ adsorbs to mixed phosphatidylcholine (PC)/phosphatidylglycerol (PG) membranes with an endothermic reaction enthalpy of δH- + 0 · 1 kcal/mol. La³⁺ binds to sonified PC vesicles with a reaction enthalpy of δH- +1 · 8 kcal/mol. The binding constants are of the order of 10 m”1 for Ca²⁺ and 4×10³ m^-1 for La^{3 +}. The role of lipids in the random coil=β-sheet equilibrium of different types of Alzheimer model peptides was investigated with circular dichroism (CD) and high sensitivity titration calorimetry. Alzheimer peptide βAP(1–40)OH and several fragments of this peptide undergo a concentration-dependent, co-operative random coil=β-sheet transition in solution which can be described by a linear association model with a nucleation parameter σ-0.2–0.01 and a growth parameter s-10⁴ M^-1. Addition of sonified lipid vesicles containing negatively charged lipids shifts the equilibrium towards the β-sheet conformation. This can be explained by an aggregation phenomenon at the lipid/water interphase. The cationic peptides are attracted to the negatively charged membrane surface causing a local increase in peptide concentration. The high peptide concentration, together with the ordering of the peptide molecules on the membrane surface, facilitates β-sheet formation, constituting the first experimental evidence for the induction of β-sheet formation via the membrane surface. The binding of Alzheimer peptide fragments to the lipid membrane is accompanied by an exothermic heat of reaction with δH in the range - 2- - 8 kcal/mol.

Key Words:

• Random coil-β-sheet transition
• lipid-peptide interaction
• Alzheimer peptide
• calcium ion
• lanthanum ion