The assembly of protein strands into fibrils

Apr 11, 2010
The assembly of protein strands into fibrils
Numerical simulations show left-handed helices of Amyloid-Fibers consisting of beta-Lactoglobulin proteins (Picture: Prof. R. Mezzenga, ETH Zurich)

Researchers at ETH Zurich, EPF Lausanne and at the University of Fribourg have evidenced a basic general mechanism describing how filamentous proteins assemble into ribbon like structures, the so-called Amyloid fibrils. Combining experiments and theory, they could explain how denatured milk proteins assemble into ribbon like structures composed of up to five filaments. These findings are shining a surprisingly new light on the assembly of these proteins.

The depicts on its screen the few nanometer thick and few long as white flexible sticks, crisscrossing the surface on which they are deposited. The very peculiar property of these proteins lies in fact that they can self assemble into complex ribbon-like twisted fibers.

Researchers at ETH Zürich, EPF Lausanne and University of Fribourg have teamed up to take images of the fibers and to analyze them using concepts from polymer physics and theoretical modeling. This combination of expertise has lead them to propose a set of general rules governing the assembly of filaments into thicker and twisted ribbon like fibers. Their results are published in the current issue of the scientific journal Nature Nanotechnology.

"The model that we propose is extremely precise in its predictions", says Raffaele Mezzenga, Professor of Food and Soft Materials Sciences at the ETH Zürich. "Up to now there was no such exact and general model for the formation of Amyloid fibers", continues Giovanni Dietler, Professor of Physics of Living Matter, at the EPF Lausanne.

The structure of the Amyloid fibers as it was unveiled by the experiments, surprised the researchers. Single proteins build the long filaments and subsequently the filaments assemble side by side to form the ribbon-like twisted fibers.

Mezzenga explains that the ribbon-like structure is the logic consequence of the strong charge carried by the building blocks of the fibers. In fact, the single proteins feel a strong mutual repulsion preventing them to pack and the ribbon structure is the only one that permits to limit this repulsion. Presently one missing information in the present model, is the exact nature of the short range attraction between the building blocks that drives in the first place the assembly among the filaments. Scientists agree that along the filaments there are charge-less domains of hydrophobic character (water repellant) that are the source of the short-range attraction. So there is a balance between attractive and repulsive interactions and the results is the ribbon like twisted conformation.

Self-organizing proteins are common in living matter and they are found in large aggregates for example in blood coagulation. Spherical like proteins are used in food industry as emulsifiers, gelling and foaming agents and in vitro they form Amyloid like structures. These latter fibers have properties (elasticity, solubility, etc) favorable for food texturing or to produce special structures. The milk protein beta-lactoglubulin studied by Mezzenga and his colleagues is at the beginning spherical and by a heat treatment accompanied by acid environment it aggregates into the filamentous structures. Beta-lactoglobulin is an important component of the milk serum and therefore very relevant for food industry.

The knowledge gained by the scientists on this food protein can potentially benefit medical sciences. In fact Amyloid-like fibers appear in humans affected by neurodegenerative diseases, like Alzheimer- or Creutzfeldt-Jakob disease. These human fibers, although made out of a very different proteins, are also ribbon-like and twisted and their assembly into long aggregates is presently under intense scrutiny. The model proposed by the team could also help to understand the genesis and development of theses diseases.

Explore further: Vegetable oil ingredient key to destroying gastric disease bacteria

More information: Adamcik J, Jung J-M, Flakowski J, De Los Rios P, Dietler G, Mezzenga R. Understanding Amyloid Aggregation by Statistical Analysis of Atomic Force Microscopy Images. Nature Nanotechnology. 2010, Advance online publication 11 April 2010. doi:10.1038/NNANO.2010.59

Provided by Ecole Polytechnique Fédérale de Lausanne

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

Researchers link metal ions to neurodegenerative disease

Aug 06, 2007

A multi-institutional team of researchers led by Emory University has defined for the first time how metal ions bind to amyloid fibrils in the brain in a way that appears toxic to neurons. Amyloid fibrils are linked to the ...

Destroying amyloid proteins with lasers

Jan 07, 2009

Researchers have found that a technique used to visualize amyloid fibers in the laboratory might have the potential to destroy them in the clinic. The technique involves zapping the fluorescently-tagged fibers with a laser, ...

Yeast model shows promise as Alzheimer's test

Nov 18, 2006

A century ago this month, German psychiatrist Alois Alzheimer formally described characteristics of the neurodegenerative disease which ultimately came to bear his name. While international efforts to learn about Alzheimer's ...

Alzheimer's prevention role discovered for prions

Jul 03, 2007

A role for prion proteins, the much debated agents of mad cow disease and vCJD, has been identified. It appears that the normal prions produced by the body help to prevent the plaques that build up in the brain to cause Alzheimer’s ...

Recommended for you

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.