The polyphenol EGCG inhibits amyloid formation less efficiently at phospholipid interfaces than in bulk solution.
Age-related diseases, like Alzheimer's disease and type 2 diabetes mellitus, are characterized by protein misfolding and the subsequent pathological deposition of fibrillized protein, also called amyloid. Several classes of amyloid-inhibitors have recently been tested, traditionally under bulk conditions. However, it has become apparent that amyloid fibrils and oligomers assemble and exert their cytotoxic effect at cellular membranes, rather than in bulk solution. Knowledge is therefore required of inhibitor activity specifically at the phospholipid membrane interface. Here we show, using surface-specific sum-frequency generation (SFG) spectroscopy and atomic force microscopy (AFM), that the commonly used (-)-epigallocatechin gallate (EGCG) is a much less efficient amyloid inhibitor at a phospholipid interface than in bulk solution. Moreover, EGCG is not able to disaggregate existing amyloid fibrils at a phospholipid interface, in contrast to its behavior in bulk. Our results show that interfaces significantly affect the efficiency of inhibition by EGCG inhibitors and should therefore be considered during the design and testing of amyloid inhibitors.
FOM Institute AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands.
Maarten F M
MF
Engel
Corianne C
CC
vandenAkker
Michael
M
Schleeger
Krassimir P
KP
Velikov
Gijsje H
GH
Koenderink
Mischa
M
Bonn
D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D015394:Molecular Structure; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D012996:Solutions; D013057:Spectrum Analysis; D013499:Surface Properties
D058228:Islet Amyloid Polypeptide; D010743:Phospholipids; D059808:Polyphenols; D012996:Solutions; D002392:Catechin; C045651:epigallocatechin gallate