Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides
| Authors | |
|---|---|
| Year of publication | 2014 |
| Type | Article in Periodical |
| Magazine / Source | Journal of the American Chemical Society |
| MU Faculty or unit | |
| 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. |
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