Amyloid Fibrils

Amyloid fibrils represent a class of peptide structures characterized by a cross-beta sheet quaternary structure of the amino acids, with beta-strands stacked perpendicular to the axis of the fibril.

While polypeptide aggregation and amyloid assembly historically has been associated with protein folding disorders, like Alzheimer's disease (Aβ peptide aggregation) or Parkinson's disease (α-synuclein aggregation), amyloid is also abundant in nature for functional purposes, where the high-density packing of amino acids, its unique mechanical or its chemical properties allows a highly adapted use. Fibrillar deposits and amyloidal structures thus serve a useful purpose for the formation of bacterial biofilm, natural adhesives, fungal spore production, melansome production in the skin, as well as hormone packing in the secretory granules of the endocrine system.

Amyloid fibrils are interesting biotechnological role models, and their adaptation holds great promise. The commercialization thereof, however, requires a thorough understanding of the molecular structures and mechanisms responsible for their functional properties. By comparing well-studied in-vivo functional amyloid systems to their in-vitro analogues, as well as to other non-functional in-vitro examples, we aim to investigate the functional properties of amyloid from the single molecule level. Specifically we study the secreted amyloidal curli fibrils from biofilm, their recombinant analogues (and mutants), as well as the mechanics of alpha synuclein fibrils.

Figure 1: Various species of amyloid fibrils imaged using AC mode AFM under buffer conditions. (a) Curli situated in E.coli biofilm (10µm x 10µm), (b) fibrils from recombinant csgA provided courtesy of Dr. Paul Barker, University of Cambridge, UK (350nm x 350nm), (c) and mature Wild-Type Alpha-Synuclein intertwining fibrils.

Amyloid-based Adhesives

We have discovered that nature has optimised the use of the nanoscale structural properties of amyloid fibrils to produce natural adhesives tailored for environmental success across a wide range of natural environments. By measuring the nanoscale mechanical responses of these structures, we have found amyloid to play an important mechanical role in many natural adhesives by providing both adhesive and cohesive strength. We have found this strategy utilized by otherwise unrelated organisms including bacteria (curli), algae (Chlorophyta) and a marine invertebrate (Entobdella soleae), thereby making the first ever mechanistic connection identified between the natural adhesives of very different organisms. To date, we have identified amyloid in both temporary and permanent natural adhesives, and in adhesives that cure in different environments such as moist surfaces of terrestrial habitats, and those fully submerged in seawater.

Our measurements further elucidated that important differences exist between amyloid fibrils in different natural adhesives. This has provided a unique insight as to how to approach biomimicry of amyloid-based synthetic adhesives in order to obtain specific adhesives with specific bonding capabilities to suit different applications. Click here for information about our technology development.

Patent applications filed with regards to this work: WO/2007/105190; US 2007/0266892
Figure 2: (a) Schematic model of the mechanical manipulation of single intermolecular beta-sheets of an amyloid fibril by an AFM tip. The sequential unfolding of individual molecules corresponds to the repetitive sawtooth peaks in our force-extension curves. (b) Representative force-extension curve sawtooth from probing the adhesive of the aeroterrestrial green alga, Prasiola linearis. The regularly spaced, highly-ordered peaks have been fitted to the worm-like chain model. (c) AFM image of functional amyloid fibrils in the adhesive extruded from the marine parasite, Entobdella soleae, which attaches to the skin of the common sole (Solea solea) in the marine environment.

Amyloid interactions with model membranes

Alzheimer's Disease (AD) is the most common cause of dementia in the elderly. The hallmarks of this disease consist of senile plaques composed of Amyloid beta (Aβ), neurofibrillary tangles and extensive neuronal degeneration. Aβ peptides are important components of plaques in Alzheimer's disease and among them Aβ (1-40) and Aβ (1-42) are the most common. Traditionally, insoluble plaques and fibrils of Aβ were believed to be responsible for the neurological degeneration observed in AD. However, more recent studies show that small diffusible non-fibrillar oligomers of Aβ as well as intermediate species formed during Aβ fibrillation (protofibrils) are also toxic to cultured neurons and considered to be one of the major contributing factors to the development of Alzheimer's disease. In Parkinson's disease (PD), the aggregation of α-synuclein from monomers via oligomeric intermediates to fibers is considered causative for the neuron degradation associated with the pathological condition.

The project will provide insights on the morphology and dynamics of the interaction among amyloid monomers and oligomers with model lipid membranes mimicking the so-called raft system. Lipid rafts are commonly defined as cholesterol- and sphingolipid-enriched membrane microdomains that serve as organizing centers for assembly of signaling molecules, influence membrane fluidity and trafficking of membrane proteins, and regulate different cellular processes such as neurotransmission and receptor trafficking. Using AFM we will investigate the molecular interaction of nanometers-height Aβ (1-40) monomers revealing the role played by cholesterol in the specific interaction raft system - monomers. The project will be able to shed light on the membrane toxicity of Aβ (1-40) monomers and oligomers. In PD, neuron toxicity is suggested driven by membrane pore formation, membrane thinning or direct membrane disruption, amongst others. We aim to investigate the structure-toxicity relationship within a model membrane context, starting at the single molecule level using a well-defined library of monomeric and oligomeric α-synuclein variants.

Figure 3: (a) Wild Type Alpha-Synuclein monomers on mica imaged in PBS (AC Mode, 300nm x 300nm), (b) Beta amyloid monomers on mica imaged in sodium phosphate (AC mode, 250nm x 250nm), (c) DOPC, Sphingomyelin, and Cholesterol on mica imaged in sodium phosphate (AC mode, 5µm x 5µm).

Group members involved in aspects of this project

Dr Anika Mostaert

Dr Mads Bruun Hovgaard

Padraig Keane

External project collaborators

Dr Paul Barker, University of Cambridge, UK

Dr Ine Segers-Nolten, University of Twente, The Netherlands

Prof. Dr. Roland Riek, ETH Zürich, Switzerland

Funding Sources

Science Foundation Ireland Logo


  1. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis, Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., Glabe, C. G., Science, 300, 486–489, (2003).
  2. Nanoscale Mechanical Characterisation of Amyloid Fibrils Discovered in a Natural Adhesive, Mostaert, A. S., Higgins, M. J., Fukuma, T., Rindi, F., and Jarvis, S. P., Journal of Biological Physics, 32, 393-401, (2007).
  3. Molecular biology and genetics of Alzheimer's disease, St George-Hyslop P. H., Petit, A., Comptes Rendus Biologies, 328, 119–130, (2005).
  4. Characterisation of Amyloid Nanostructures in the Natural Adhesive of Unicellular Subaerial Algae, Mostaert, A. S., Giordani, C., Crockett, R., Karsten, U., Schumann, R., and Jarvis, S. P., The Journal of Adhesion, 85, 465-483, (2009).
  5. Functional Amyloids As Natural Storage of Peptide Hormones in Pituitary Secretory Granules, Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., and Riek, R., Science, 325, 328-332, (2009).
  6. Amyloid-[beta] protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory, Shankar, G. M., Li, S., Mehta, T.H., Garcia-Munoz, A., Shepardson, N. E., et al., Nature Medicine, 14, 837–842, (2008).
  7. Mechanically functional amyloid fibrils in the adhesive of a marine invertebrate as reveled by raman spectroscopy and atomic force microscopy, Mostaert, A. S., Crockett, R., Kearn, G., Cherney, I., Gazit, E., Serpell, L. C. and Jarvis, S. P., Archives of Histology and Cytology, 72, 4/5, 199-207, (2009).
  8. Characterisation of Amyloid Nanostructures in the Natural Adhesive of Unicellular Subaerial Algae, Mostaert, A. S., Giordani, C., Crockett, R., Karsten, U., Schumann, R., and Jarvis, S. P., The Journal of Adhesion, 85, 465-483, (2009).