Kinetics of adsorption of beta-amyloid peptide Abeta(1-40) to lipid bilayers.
The Alzheimer's disease-related peptide beta-amyloid (Abeta) is toxic to neurons. The toxicity of the peptide appears to require conversion of the monomeric form to an aggregated fibrillar species. The interaction of Abeta with cell membranes has attracted interest as one plausible mechanism by which the peptide exerts its toxic activity. We developed two methods to measure the adsorption of fresh (monomeric) and aged (aggregated) Abeta to lipid bilayers. In one method, the kinetics of Abeta adsorption and desorption to liposomes deposited onto a dextran-coated surface was measured using surface plasmon resonance. In the other method, Abeta was contacted with liposome-coated magnetic beads; adsorbed Abeta was separated from solution-phase peptide by use of a magnetic field. Monomeric Abeta adsorbed quickly but reversibly to lipid bilayers with low affinity, while aggregated Abeta adsorbed slowly but irreversibly. These two methods provide complementary means of quantifying the adsorption of aggregating proteins to membranes. The results correlate strongly with previous observations that fibrillar, but not monomeric, Abeta restricts the motion of acyl tails in phospholipid bilayers. The methods should be useful for further elucidation of the role of membrane adsorption in mediating Abeta toxicity, and in the search for inhibitors of toxicity.
Kremer
John J
JJ
Department of Chemical Engineering, University of Wisconsin-Madison, Madison, WI 53706-1607, USA.
Murphy
Regina M
RM
D000327:Adsorption; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D046911:Macromolecular Substances; D008280:Magnetics; D008567:Membranes, Artificial; D008863:Microspheres; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D020349:Surface Plasmon Resonance / Q000379:methods*
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)