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 delta H approximately +0.1 kcal/mol. La3+ binds to sonified PC vesicles with a reaction enthalpy of delta H approximately + 1.8 kcal/mol. The binding constants are of the order of 10 M-1 for Ca2+ and 4 x 10(3) M-1 for La3+. The role of lipids in the random coil<-->beta-sheet equilibrium of different types of Alzheimer model peptides was investigated with circular dichroism (CD) and high sensitivity titration calorimetry. Alzheimer peptide beta AP(1-40)OH and several fragments of this peptide undergo a concentration-dependent, co-operative random coil<-->beta-sheet transition in solution which can be described by a linear association model with a nucleation parameter sigma approximately 0.2-0.01 and a growth parameter s approximately 10(4) M-1. Addition of sonified lipid vesicles containing negatively charged lipids shifts the equilibrium towards the beta-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 beta-sheet formation, constituting the first experimental evidence for the induction of beta-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 delta H in the range -2 - -8 kcal/mol.