Polymer-Peptide Conjugates Convert Amyloid into Protein Nanobundles through Fragmentation and Lateral Association

ACS Applied Nano Materials
John W SmithQian Chen

Abstract

The assembly of proteins into amyloid fibrils has become linked not only with the progression of myriad human diseases, but also important biological functions. Understanding and controlling the formation, structure, and stability of amyloid fibrils is therefore a major scientific goal. Here we utilize electron microscopy-based approaches combined with quantitative statistical analysis to show how recently developed kind of amyloid modulators-multivalent polymer-peptide conjugates (mPPCs)-can be applied to control the structure and stability of amyloid fibrils. In doing so, we demonstrate that mPPCs are able to convert 40-residue amyloid beta fibrils into ordered nanostructures through a combination of fragmentation and bundling. Fragmentation is shown to be consistent with a model where the rate constant of fibril breakage is independent of the fibril length, suggesting a local and specific interaction between fibrils and mPPCs. Subsequent bundling, which was previously not observed, leads to the formation of sheet-like nanostructures which are surprisingly much more uniform than the starting fibrils. These nanostructures have dimensions independent of the molecular weight of the mPPC and retain the molecular-level ordering of...Continue Reading

References

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P WestermarkC Betsholtz
Oct 3, 1999·Methods in Enzymology·L C SerpellM Sunde
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·A AggeliN Boden
Apr 12, 2003·Physical Review Letters·M S TurnerR Josephs
Jul 13, 2004·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·M Hosek, J X Tang
Sep 21, 2004·Biophysical Journal·Xueping Yu, A E Carlsson
Sep 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Barbara J BlanchardVernon M Ingram
Sep 28, 2004·Physical Review Letters·Kun-Chun LeeMark J Stevens
Nov 19, 2004·Microscopy Research and Technique·J M ZuoI Petrov
Aug 17, 2005·Microscopy Research and Technique·Hanna Ksiezak-Reding, Joseph S Wall
May 18, 2006·Annual Review of Microbiology·Michelle M Barnhart, Matthew R Chapman
Sep 1, 2007·Chembiochem : a European Journal of Chemical Biology·Sidhartha M ChafekarWiep Scheper
Sep 8, 2007·Mathematical Biosciences·Tiia Grönholm, Arto Annila
Oct 13, 2007·Physical Review Letters·Gregory M Grason, Robijn F Bruinsma
Nov 13, 2007·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Hossein Fazli, Ramin Golestanian
Apr 17, 2008·Angewandte Chemie·Izhack Cherny, Ehud Gazit
Jan 27, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Zhenkun ZhangEric Grelet
Jul 4, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Georgina M H WilkinsMichael J Solomon
Jul 8, 2009·Protein Engineering, Design & Selection : PEDS·Wei-Feng XueSheena E Radford
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bo ChenRobert Tycko
Oct 8, 2009·The Journal of Biological Chemistry·Wei-Feng XueSheena E Radford
Dec 17, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Yuchun HanZhibo Li
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jan BieschkeErich E Wanker
Sep 28, 2010·Physical Review Letters·Yasheng YangMichael F Hagan
Apr 20, 2011·Journal of Molecular Recognition : JMR·Unige MurvaiMiklós S Z Kellermayer
Aug 17, 2011·The Journal of Chemical Physics·Samuel I A CohenTuomas P J Knowles
Aug 23, 2011·Nature Nanotechnology·Yunsheng XiaNicholas A Kotov
Nov 24, 2011·Nano Reviews·Shruti MankarSamir K Maji
May 16, 2012·Journal of Physics. Condensed Matter : an Institute of Physics Journal·K K M SweersV Subramaniam
Oct 30, 2012·Physical Review Letters·Tuomas P J KnowlesEugene M Terentjev
May 4, 2013·The Journal of Physical Chemistry. B·John S Schreck, Jian-Min Yuan
Mar 26, 2014·Journal of the American Chemical Society·Yang SongJeffrey S Moore
Dec 4, 2014·Journal of the American Chemical Society·Ti-Hsuan KuNathan C Gianneschi
Feb 27, 2015·Physical Chemistry Chemical Physics : PCCP·Paolo ArosioSara Linse
Oct 7, 2015·Trends in Microbiology·Nani Van GervenHan Remaut
Nov 2, 2015·The Journal of Chemical Physics·Thomas C T MichaelsTuomas P J Knowles
Nov 26, 2015·The Journal of Biological Chemistry·Rosa CrespoPedro M Martins
Dec 25, 2015·Journal of the American Chemical Society·Nadezhda NespovitayaRoland Riek
Jan 9, 2016·Biophysical Journal·Huafeng Xu, David E Shaw
Mar 29, 2016·Nature Structural & Molecular Biology·Marcus D TuttleChad M Rienstra
Mar 31, 2016·EMBO Molecular Medicine·Dennis J Selkoe, John Hardy

❮ Previous
Next ❯

Citations

Jul 9, 2020·Nanoscale·Nicholas AndrikopoulosPu Chun Ke
Aug 25, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·John W Smith, Qian Chen
Nov 19, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Marie RütterAyelet David

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.