Amyloid Oligomer Formation Probed by Water Proton Magnetic Resonance Spectroscopy

• Published in: Biophysical journal Vol. 100; no. 9; pp. 2302 - 2308
• Main Authors: Walton, J.H., Berry, R.S., Despa, F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.05.2011; Biophysical Society; The Biophysical Society
• Subjects: amyloid; Amyloid - chemistry; Amyloid - ultrastructure; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - ultrastructure; antibodies; Austenitic stainless steels; Biophysics; blood serum; computer simulation; Diseases; Electron microscopes; electron microscopy; Hydrophobic surfaces; hydrophobicity; image analysis; immunochemistry; Immunohistochemistry; Magnetic relaxation; Magnetic Resonance Spectroscopy; nuclear magnetic resonance spectroscopy; Oligomers; Peptides; Pharmacology; Protein; Protein Structure, Quaternary; Proton magnetic resonance; Protons; Serums; Spectroscopy; Spectrum analysis; Surface Properties; Time Factors; toxicity; Water; Water - chemistry
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2011.03.029

Formation of amyloid oligomers, the most toxic species of amyloids in degenerative diseases, is critically coupled to the interplay with surrounding water. The hydrophobic force driving the oligomerization causes water removal from interfaces, changing the surface-hydration properties. Here, we show that such effects alter the magnetic relaxation response of local water in ways that may enable oligomer detection. By using water proton magnetic resonance spectroscopy, we measured significantly longer transverse magnetic relaxation ( T 2) times in mixtures of serum and amyloidogenic A β 1-42 peptides versus similar concentration solutions of serum and nonamyloidogenic scrambled A β 42-1 peptides. Immunochemistry with oligomer-specific antibodies, electron microscopy and computer simulations demonstrated that the hyperintense magnetic signal correlates with A β 1-42 oligomerization. Finding early biophysical markers of the oligomerization process is crucial for guiding the development of new noninvasive imaging techniques, enabling timely diagnosis of amyloid-related diseases and pharmacological intervention.