Amyloid fibrils as functional nanomaterials

Published on December 31, 2017   39 min

A selection of talks on Biochemistry

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My name is Juliet Gerrard, and I'm from the University of Auckland. And today I'd like to tell you about amyloid fibrils as functional Nanomaterials. You've heard something about amyloid fibrils from other lectures in this series, but today, rather than focus on their role in the body or in disease, I'll be talking you through how you might think of them as a useful material to use outside the body for a whole range of application.
So, as an outline of my talk, I'll start up just to orient you and take you through what amyloid fibrils are and how and why we want to make them. And I'll just give you a quick taste of the sorts of applications that are being developed for these materials worldwide. Then I'll focus on our efforts in my lab to generate amyloid fibrils from readily available sustainable sources. And I'll give you a couple of examples of applications that we've worked on in my lab that really exemplify the strengths of these materials. First of all as a nanoscaffold for enzyme immobilisation and then as a template for nanowires and biosensors.
So, in this slide, I've given you a very simple picture of protein folding and misfolding inside and outside the cell. So, if you start on the left of the slide that's where you can imagine the protein being synthesized on the ribosome and the polypeptide chain leaves the ribosome unfolded, but very quickly starts to fold into a variety of different folded forms. Moving down the diagram, you can see the intermediate folded states. And the states that coalesce into the native form, which of course could be oligomeric protein in vivo or it could be a fiber. In the laboratory, we spend a lot of time trying to make sure that the protein stays in that native form or folds into it if we're expressing it recombinantly. And we try to avoid the disordered aggregates that you can see forming on the periphery of the slide. When we tried to make an amyloid fibril, what we do is try to slightly destabilize the native form to get back to the intermediate folded state and form the prefibrillar species that go on to form the amyloid fibrils. Beyond this, if we want the amyloid fibrils to be used outside the cell, we would like them to form bigger structures. I've emphasized this point. In many ways this is more of an art than a science, as we screen lots of different conditions to try to find the right ones to do hierarchical assembly. So, the ideal process would be to start with a native protein or an unfolded protein, but it tends to be easier from the native form, destabilize it slightly, and managed to capture the amyloid fibrils in solution conditions that are predisposed to form those biggest structures.