Effects of Amyloid Beta Peptides on the Lysis Tension of Lipid Bilayer Vesicles Containing Oxysterols

¹ La Jolla Bioengineering Institute

^* To whom correspondence should be addressed. E-mail: frangos{at}ljbi.org.

Submitted on June 13, 2007
Revised on July 24, 2007
Accepted on 7 November 2007

	Abstract

Amyloid beta peptides (A) applied directly from solution to model lipid membranes produced dramatic changes in the material properties of the bilayer when certain oxysterols were present in the bilayer. These effects were dependent on both lipid and peptide composition, and occurred at peptide concentrations as low as 100 nM. Using micropipette manipulation of giant unilamellar vesicles, we directly measured the lysis tension of lipid bilayers of various compositions. 1-stearoyl-2-oleoyl-sn glycero-3-phosphocholine (SOPC) constituted the main lipid component at 70 mole percent, with the remaining 30 mole percent comprised of pure or mixed sterols: cholesterol (CHOL), 7-ketocholesterol (KETO), or 7-hydroxycholesterol (OHCHOL). SOPC:CHOL bilayers did not exhibit significant changes in mechanical properties after exposure to either A(1-42) or A(1-40). Partial substitution of CHOL with KETO (5 mole percent), however, caused a drastic reduction of the lysis tension after exposure to A(1-42), but not A(1-40). Partial substitution of CHOL with OHCHOL (5 mole percent) caused a drastic reduction of the lysis tension after exposure to A(1-40) as well as to A(1-42). We attribute the effect to the reduction in intermolecular cohesive interactions caused by the presence of the second dipole of oxysterols, which reduces the energetic barrier for A insertion into the bilayer.

Key Words: amyloid beta peptides, lipid bilayers, oxysterols