Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides

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Authors	VÁCHA Robert LINSE S. LUND M.
Year of publication	2014
Type	Article in Periodical
Magazine / Source	Journal of the American Chemical Society
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://pubs.acs.org/doi/abs/10.1021/ja505502e
Doi	http://dx.doi.org/10.1021/ja505502e
Field	Physical chemistry and theoretical chemistry
Keywords	BETA PROTEIN FIBRILLATION; ALPHA-SYNUCLEIN; POLYMERIC NANOPARTICLES; MEMBRANE INTERACTIONS; LIPID-BILAYERS; DRUG-DELIVERY; PHASE; NUCLEATION; INHIBITION; INTERFACES
Description	The presence of surfaces influences the fibril formation kinetics of peptides and proteins. We present a systematic study of the aggregation kinetics of amyloidogenic peptides caused by different surfaces using molecular simulations of model peptides and thioflavin T fluorescence experiments. Increasing the monomer surface attraction affects the nucleation and growth of small oligomers in a nonlinear manner: Weakly attractive surfaces lead to retardation; strongly attractive surfaces lead to acceleration. Further, the same type of surface either accelerates or retards growth, depending on the bulk propensity of the peptide to form fibrils: An attractive surface retards fibril formation of peptides with a high tendency for fibril formation, while the same surface accelerates fibril formation of peptides with a low propensity for fibril formation. The surface effect is thus determined by the relative association propensity of peptides for the surface compared to bulk and by the surface area to protein concentration ratio. This rationalization is in agreement with the measured fibrillar growth of a-synuclein from Parkinson and amyloid beta peptide from Alzheimer disease in the presence of surface area introduced in a controlled way in the form of nanoparticles. These findings offer molecular insight into amyloid formation kinetics in complex environments and may be used to tune fibrillation properties in diverse systems.
Related projects:	CEITEC - Central European Institute of Technology SYLICA - Synergies of Life and Material Sciences to Create a New Future Self-assembly of amphiphilic peptides with helical character