More than a century after the first description of amyloids by Alois Alzheimer, and despite the enormous research efforts since then, the field is still full of surprises. While searching for answers to questions for example on the driving force, mechanism, and regulation of amyloidogenesis, or on the structure, physiological and pathological roles of different amyloid aggregates, unexpected properties are regularly revealed, broadening their application possibilities. This Collection aims to focus on the beneficial sides of amyloid formation, primarily exploring the potential use of amyloids in material science, bioengineering, and synthetic chemistry.
Amyloids are versatile multifaceted self-assembled nanomaterials. Alois Alzheimer described them first in his 1907 paper as insoluble plaques found in the postmortem brain of a dementia patient. He named these ‘amyloids’ referring to carbohydrates, but later the deposits were proven to primarily consist of proteins1,2. Since then misfolded amyloid-like protein deposits have been identified as hallmarks of several human diseases. Of these, the aging related Alzheimer’s disease (AD) remained the most extensively studied as it affects the largest population of patients and represents dramatically increasing personal and societal problems. The controversial amyloid hypothesis has been both widely used and a frequently debated model in AD research3,4. Meanwhile, new amyloids appear everywhere; more recently amyloidogenic sequences of the viral SARS-CoV-2 spike protein were identified and hypothesized as a potential contributing factor to long COVID-19 symptoms in the ongoing pandemic5. In addition, amyloidogenesis, the formation of these highly ordered protein aggregates with common physicochemical properties, seems to be a general feature of all polypeptides including even common globular proteins6. Recently, amyloid-like assemblies of simple metabolites have also been reported7.
While pathological amyloids are being associated with a growing number of diseases; non-pathological forms also appear in many organisms performing a wide range of normal physiological functions ranging from hormone storage to structural support and defense mechanisms6,8. In addition, self-assembly of peptides gains a growing interest in synthetic chemistry, bioengineering and material science as these aggregates can serve as a simple, low cost, green, and tuneable catalysts of chemical reactions or scaffolds and building blocks for nano/biomaterials. The highly stable, ordered, and customizable amyloid aggregates can be applied as templates to produce various nanomaterials or used as biomimetic catalysts9,10,11. Despite the extensive efforts and vast amount of results reported on amyloids, especially on those formed from peptides/proteins of biomedical importance (e.g., amyloid-β, tau, α-synuclein, prions, insulin), the structural characterization of the intermediates/fibrils and understanding the driving force, mechanism, or modulation opportunities of the self-assembly in a particular amyloidogenic system remained challenging. The transient nature of the intermediates, branched, nonlinear aggregation pathways, and polymorphism of fibrils are just a few examples of the many arising complications12,13,14,15,16. These difficulties somewhat limit widespread synthetic applications in practice at present.
The following papers in this Collection give a glance at recent research efforts trying to solve the mysteries of amyloid formation and explore new, exciting features that could broaden the scope of future applications. It includes papers that focus directly on potential applications of amyloids as well as those with rather biology/disease-oriented emphasis that shed light on properties that could be exploited by follow-up studies. For example, Vergunst and Langelaan17 identified structural features influencing the self-assembly of hydrophobins, small natural proteins secreted by fungi, that could be functionalized into commercial green emulsifiers or surface modifying agents for health-, food- or other industries. Another interesting application of engineered amyloid curli fibers from E. coli was presented by Saldanha et al.18. Using amyloids as scaffolds fused with a pH-responsive fluorescent protein, and trapping in a textile matrix, the resulting biosynthesized amyloid-based textile-composites can be used as potential wearable pH sensor skin patches for healthcare and fitness industries. The amyloidogenic 21-29 fragment of β2-microglobulin (β2m21–29) was proposed by Tseng et al.19 as a potential framework for functional biopolymers that could alternate between parallel and anti-parallel β-sheet structures in response to pH-changes. Biverstål and co-workers20 developed a generic approach using Bri2 BRICHOS-based fusion proteins to decorate amyloid fibrils with functional proteins for applications in cell culture, tissue engineering, drug delivery, etc. Finally, Schiattarella et al.21 aimed to decipher the origin of the unexpected intrinsic photoluminescence exhibited by amyloid-like systems.
As illustrated by all these articles among others, amyloids are ubiquitous and highly customizable. While biomedical, structural, and mechanistic investigations will remain important in the field, future developments will likely be directed toward more catalytic and material science applications.
References
Stelzmann, R. A., Schnitzlein, H. N. & Murtagh, H. F. An English Translation of Alzheimer’s 1907 Paper, “Über eine eigenartige Erkankung der Hirnrinde”. Clin. Anat. 8, 429–431. https://doi.org/10.1002/ca.980080612(1995) (1995).
Lansbury, P. T. A reductionist view of Alzheimer’s disease. Acc. Chem. Res. 29, 317–321. https://doi.org/10.1021/ar950159u (1996).
Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 8, 595–608. https://doi.org/10.15252/emmm.201606210 (2016).
Piller, C. Blots on a field?. Science 377, 358–363. https://doi.org/10.1126/science.add9993 (2022).
Nyström, S. & Hammarström, P. Amyloidogenesis of SARS-CoV-2 spike protein. J. Am. Chem. Soc. 144, 8945–8950. https://doi.org/10.1021/jacs.2c03925 (2022).
Chiti, F. & Dobson, C. M. Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade. Annu. Rev. Biochem. 86, 27–68. https://doi.org/10.1146/annurev-biochem-061516-045115 (2017).
Gour, N. & Gazit, E. Metabolite assemblies: A surprising extension to the amyloid hypothesis. Curr. Opin. Chem. Biol. 64, 154–164. https://doi.org/10.1016/j.cbpa.2021.07.005 (2021).
Brown, A. & Török, M. Functional amyloids in the human body. Bioorg. Med. Chem. Lett. 40, 127914. https://doi.org/10.1016/j.bmcl.2021.127914 (2021).
Perrett, S. et al. (eds) Biological and Bio-inspired Nanomaterials Properties and Assembly Mechanisms. Advances in Experimental Medicine and Biology Vol. 1174 (Springer, 2019).
Wei, G. et al. Self-assembling peptide and protein amyloids: From structure to tailored function in nanotechnology. Chem. Soc. Rev. 46, 4661–4708. https://doi.org/10.1039/C6CS00542J (2017).
Han, J., Gong, H., Ren, X. & Yan, X. Supramolecular nanozymes based on peptide self-assembly for biomimetic catalysis. Nano Today 41, 101295. https://doi.org/10.1016/j.nantod.2021.101295 (2021).
Iadanza, M. G., Jackson, M. P., Hewitt, E. W., Ranson, N. A. & Radford, S. E. A new era for understanding amyloid structures and disease. Nat. Rev. Mol. Cell. Biol. 19, 755–773. https://doi.org/10.1038/s41580-018-0060-8 (2018).
Michaelis, T. C. T. et al. Chemical kinetics for bridging molecular mechanisms and macroscopic measurements of amyloid fibril formation. Annu. Rev. Phys. Chem. 69, 273–298. https://doi.org/10.1146/annurev-physchem-050317-021322 (2018).
Almeida, Z. L. & Brito, R. M. M. Structure and aggregation mechanisms in amyloids. Molecules 25, 1195. https://doi.org/10.3390/molecules25051195 (2020).
Buell, A. K. Stability matters, too: The thermodynamics of amyloid fibril formation. Chem. Sci. https://doi.org/10.1039/D1SC06782F (2022).
Annamalai, K. et al. Polymorphism of amyloid fibrils in vivo. Angew. Chem. Int. Ed. 55, 4822–4825. https://doi.org/10.1002/anie.201511524 (2016).
Vergunst, K. L. & Langelaan, D. N. The N-terminal tail of the hydrophobin SC16 is not required for rodlet formation. Sci. Rep. 12, 366. https://doi.org/10.1038/s41598-021-04223-6 (2022).
Saldanha, D. J., Abdali, Z., Modafferi, D., Janfeshan, B. & Courchesne, N. M. D. Fabrication of fluorescent pH-responsive protein–textile composites. Sci. Rep. 10, 13052. https://doi.org/10.1038/s41598-020-70079-x (2020).
Tseng, W. H., Chen, S. H. & Hiramatsu, H. pH-controlled stacking direction of the β-strands in peptide fibrils. Sci. Rep. 10, 22199. https://doi.org/10.1038/s41598-020-79001-x (2020).
Biverstål, H. et al. Functionalization of amyloid fibrils via the Bri2 BRICHOS domain. Sci. Rep. 10, 21765. https://doi.org/10.1038/s41598-020-78732-1 (2020).
Schiattarella, C. et al. Solid-state optical properties of self-assembling amyloid-like peptides with different charged states at the terminal ends. Sci. Rep. 12, 759. https://doi.org/10.1038/s41598-021-04394-2 (2022).
Acknowledgements
Many thanks to all Contributors to the Collection.
Author information
Authors and Affiliations
Contributions
M. T. wrote the invited editorial.
Corresponding author
Ethics declarations
Competing interests
The author declares no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Török, M. Amyloids in synthetic applications. Sci Rep 12, 21095 (2022). https://doi.org/10.1038/s41598-022-25499-2
Published:
DOI: https://doi.org/10.1038/s41598-022-25499-2
