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

Abstract

Amyloid beta-peptides (Abeta) 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. The glycerophospholipid 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) constituted the main lipid component at 70 mol %. The remaining 30 mol % was composed of the following pure or mixed sterols: cholesterol (CHOL), 7-ketocholesterol (KETO), or 7beta-hydroxycholesterol (OHCHOL). SOPC/CHOL bilayers did not exhibit significant changes in mechanical properties after exposure to either Abeta(1-42) or Abeta(1-40). Partial substitution of CHOL with KETO (5 mol %), however, caused a drastic reduction of the lysis tension after exposure to Abeta(1-42) but not to Abeta(1-40). Partial substitution of CHOL with OHCHOL (5 mol %) caused a drastic reduction of the lysis tension after exposure to Abeta(1-40) and to Abeta(1-42). We attribute these effects to the reduction in intermolecular cohesive interactions caused by the presence of the second dipole of oxysterols, which reduces the energetic barrier for Abeta insertion into the bilayer.

Formation of Giant Unilamellar Proteo-Liposomes by Osmotic Shock

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Biophysical Insights into How Surfaces, Including Lipid Membranes, Modulate Protein Aggregation Related to Neurodegeneration

“…Studies performed on supported phospholipid membranes revealed that exposure to Aβ modifies morphology and local mechanical properties of bilayers, reducing the force required to break through the membrane with an AFM probe (Dante et al, 2011). The lysis tension of unilamellar vesicles containing oxysterols are altered by exposure to nanomolar concentration of Aβ peptides (Kim and Frangos, 2008). Collectively, these results suggest Aβ can negatively impact the mechanical integrity of lipid membranes.…”

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