An Auto-Catalytic Surface for Conformational Replication of Amyloid Fibrils-Genesis of an Amyloid World?
2011 (English)In: Origins of life and evolution of the biosphere, ISSN 0169-6149, E-ISSN 1573-0875, Vol. 41, no 4, 373-383 p.Article in journal (Refereed) Published
Amyloid fibrils are composed of self assembled stacked peptide or protein molecules folded and trapped in a stable cross-beta-sheet conformation. The amyloid fibrillation mechanism represents an intriguing self-catalyzed process rendering replication of a molecular conformational memory of interest for prebiotic chemistry. Herein we describe how a solid surface can be rendered auto-catalytic for fibrillation of a protein solution. We have discovered that a hydrophobic silicon or glass surface can be made to continuously fibrillate solutions of insulin monomers under stressed conditions (pH 1.6, 65 degrees C). It was found that the surface acts as a platform for the formation of nascent seeds that induce fibril replication on and at the surface. This autocatalytic effect stems from a layer a few insulin molecules thick representing an oligomeric layer of misfolded, conformationally trapped, insulin molecules that rapidly through epitaxial growth catalyze the rate determining step (nucleation) during fibril replication. This autocatalytic layer is generated by the protein-solid surface interaction and conformational changes of the adsorbed protein during exposure at the air-water interface. The resulting autocatalytic surface thus both initiates local conformational molecular self-replication and acts as a reservoir for fibril seeds budding off into solution spreading fibril replication entities to the surrounding medium. The possibility of catalysis of the conformational replication process by minute amounts of nucleation sites located on a recruiting surface can evade the issue of dramatic concentration dependence of amyloidogenesis.
Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2011. Vol. 41, no 4, 373-383 p.
Amyloid, Molecular replication, Self-assembly, Origin of life
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-75743DOI: 10.1007/s11084-010-9230-1ISI: 000300367300007OAI: oai:DiVA.org:liu-75743DiVA: diva2:508659
Funding Agencies|Swedish Research Council||Knut and Alice Wallenberg Foundation||Swedish Foundation for Strategic Research||2012-03-092012-03-092012-03-09