Self-folding and aggregation of amyloid nanofibrils
Amyloids are highly organized protein filaments, rich in β-sheet secondary structures that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer's Disease). Identified as natural functional materials in bacteria, in addition to their...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Royal Society of Chemistry, The
2013
|
| Online Access: | http://hdl.handle.net/1721.1/77243 https://orcid.org/0000-0002-4173-9659 |
| _version_ | 1826199886716993536 |
|---|---|
| author | Paparcone, Raffaella Cranford, Steven Wayne Buehler, Markus J. |
| author2 | Massachusetts Institute of Technology. Center for Materials Science and Engineering |
| author_facet | Massachusetts Institute of Technology. Center for Materials Science and Engineering Paparcone, Raffaella Cranford, Steven Wayne Buehler, Markus J. |
| author_sort | Paparcone, Raffaella |
| collection | MIT |
| description | Amyloids are highly organized protein filaments, rich in β-sheet secondary structures that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer's Disease). Identified as natural functional materials in bacteria, in addition to their remarkable mechanical properties, amyloids have also been proposed as a platform for novel biomaterials in nanotechnology applications including nanowires, liquid crystals, scaffolds and thin films. Despite recent progress in understanding amyloid structure and behavior, the latent self-assembly mechanism and the underlying adhesion forces that drive the aggregation process remain poorly understood. On the basis of previous full atomistic simulations, here we report a simple coarse–grain model to analyze the competition between adhesive forces and elastic deformation of amyloid fibrils. We use simple model system to investigate self-assembly mechanisms of fibrils, focused on the formation of self-folded nanorackets and nanorings, and thereby address a critical issue in linking the biochemical (Angstrom) to micrometre scales relevant for larger-scale states of functional amyloid materials. We investigate the effect of varying the interfibril adhesion energy on the structure and stability of self-folded nanorackets and nanorings and demonstrate that these aggregated amyloid fibrils are stable in such states even when the fibril–fibril interaction is relatively weak, given that the constituting amyloid fibril length exceeds a critical fibril length-scale of several hundred nanometres. We further present a simple approach to directly determine the interfibril adhesion strength from geometric measures. In addition to providing insight into the physics of aggregation of amyloid fibrils our model enables the analysis of large-scale amyloid plaques and presents a new method for the estimation and engineering of the adhesive forces responsible of the self-assembly process of amyloid nanostructures, filling a gap that previously existed between full atomistic simulations of primarily ultra-short fibrils and much larger micrometre-scale amyloid aggregates. Via direct simulation of large-scale amyloid aggregates consisting of hundreds of fibrils we demonstrate that the fibril length has a profound impact on their structure and mechanical properties, where the critical fibril length-scale derived from our analysis of self-folded nanorackets and nanorings defines the structure of amyloid aggregates. A multi-scale modeling approach as used here, bridging the scales from Angstroms to micrometres, opens a wide range of possible nanotechnology applications by presenting a holistic framework that balances mechanical properties of individual fibrils, hierarchical self-assembly, and the adhesive forces determining their stability to facilitate the design of de novo amyloid materials. |
| first_indexed | 2024-09-23T11:27:41Z |
| format | Article |
| id | mit-1721.1/77243 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:27:41Z |
| publishDate | 2013 |
| publisher | Royal Society of Chemistry, The |
| record_format | dspace |
| spelling | mit-1721.1/772432022-10-01T03:45:18Z Self-folding and aggregation of amyloid nanofibrils Paparcone, Raffaella Cranford, Steven Wayne Buehler, Markus J. Massachusetts Institute of Technology. Center for Materials Science and Engineering Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Massachusetts Institute of Technology. Laboratory for Atomistic and Molecular Mechanics Paparcone, Raffaella Cranford, Steven Wayne Buehler, Markus J. Amyloids are highly organized protein filaments, rich in β-sheet secondary structures that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer's Disease). Identified as natural functional materials in bacteria, in addition to their remarkable mechanical properties, amyloids have also been proposed as a platform for novel biomaterials in nanotechnology applications including nanowires, liquid crystals, scaffolds and thin films. Despite recent progress in understanding amyloid structure and behavior, the latent self-assembly mechanism and the underlying adhesion forces that drive the aggregation process remain poorly understood. On the basis of previous full atomistic simulations, here we report a simple coarse–grain model to analyze the competition between adhesive forces and elastic deformation of amyloid fibrils. We use simple model system to investigate self-assembly mechanisms of fibrils, focused on the formation of self-folded nanorackets and nanorings, and thereby address a critical issue in linking the biochemical (Angstrom) to micrometre scales relevant for larger-scale states of functional amyloid materials. We investigate the effect of varying the interfibril adhesion energy on the structure and stability of self-folded nanorackets and nanorings and demonstrate that these aggregated amyloid fibrils are stable in such states even when the fibril–fibril interaction is relatively weak, given that the constituting amyloid fibril length exceeds a critical fibril length-scale of several hundred nanometres. We further present a simple approach to directly determine the interfibril adhesion strength from geometric measures. In addition to providing insight into the physics of aggregation of amyloid fibrils our model enables the analysis of large-scale amyloid plaques and presents a new method for the estimation and engineering of the adhesive forces responsible of the self-assembly process of amyloid nanostructures, filling a gap that previously existed between full atomistic simulations of primarily ultra-short fibrils and much larger micrometre-scale amyloid aggregates. Via direct simulation of large-scale amyloid aggregates consisting of hundreds of fibrils we demonstrate that the fibril length has a profound impact on their structure and mechanical properties, where the critical fibril length-scale derived from our analysis of self-folded nanorackets and nanorings defines the structure of amyloid aggregates. A multi-scale modeling approach as used here, bridging the scales from Angstroms to micrometres, opens a wide range of possible nanotechnology applications by presenting a holistic framework that balances mechanical properties of individual fibrils, hierarchical self-assembly, and the adhesive forces determining their stability to facilitate the design of de novo amyloid materials. United States. Office of Naval Research (Grant NN00014-08-1-0844) National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Grant DMR-0819762) United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-09-1-0541) 2013-02-28T19:40:49Z 2013-02-28T19:40:49Z 2011-02 2010-11 Article http://purl.org/eprint/type/JournalArticle 2040-3364 2040-3372 http://hdl.handle.net/1721.1/77243 Paparcone, Raffaella, Steven W. Cranford, and Markus J. Buehler. “Self-folding and Aggregation of Amyloid Nanofibrils.” Nanoscale 3.4 (2011): 1748. https://orcid.org/0000-0002-4173-9659 en_US http://dx.doi.org/10.1039/c0nr00840k Nanoscale Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Royal Society of Chemistry, The MIT web domain |
| spellingShingle | Paparcone, Raffaella Cranford, Steven Wayne Buehler, Markus J. Self-folding and aggregation of amyloid nanofibrils |
| title | Self-folding and aggregation of amyloid nanofibrils |
| title_full | Self-folding and aggregation of amyloid nanofibrils |
| title_fullStr | Self-folding and aggregation of amyloid nanofibrils |
| title_full_unstemmed | Self-folding and aggregation of amyloid nanofibrils |
| title_short | Self-folding and aggregation of amyloid nanofibrils |
| title_sort | self folding and aggregation of amyloid nanofibrils |
| url | http://hdl.handle.net/1721.1/77243 https://orcid.org/0000-0002-4173-9659 |
| work_keys_str_mv | AT paparconeraffaella selffoldingandaggregationofamyloidnanofibrils AT cranfordstevenwayne selffoldingandaggregationofamyloidnanofibrils AT buehlermarkusj selffoldingandaggregationofamyloidnanofibrils |