On the colloidal and molecular aspects of peptide self-assembly

Peptide self-assembly is a spontaneous process, ubiquitous in nature for the creation of highly ordered and complex biological structures, making it a sought after technique in the development of novel biocompatible materials. The process is also strongly associated with various neurodegenerative diseases in the formation of amyloid plaques in diseases such as Alzheimer’s and Parkinson’s, where fully functioning proteins aggregate are reassembled into nonfunctional fibrillar aggregates that eventually lead to cell death. Understanding the underlying thermodynamics and kinetics of peptide assembly can therefore not only support the material science community, but might also lead to a deeper knowledge of biological phenomena.

In this thesis we have studied the selfassembly of the AnK model peptide, where n denotes the number of the hydrophobic amino acid alanine, A, and K is lysine that is hydrophilic. Whereas the shorter A6K assembles into hollow nanotubes, the longer A8K and A10K instead assemble into amyloidlike twisted ribbons. Although the structures macroscopically differ, using Xray and electron microscopy techniques, we show that both structures consist of the same crystalline monlayers of laminated β-sheets. From the gained structural knowledge we have devised a simple thermodynamic model describing the structures and the transition between them with increasing n.

We have further characterized the kinetics of the A8K and A10K self-assembly using NMR, spectroscopic and calorimetric techniques. The kinetics of attachment and detachment is strikingly slow. We propose that this is a general feature of β-sheet aggregates. Solutions of A8K and A10K ribbons were also investigated by rheology. The ribbons behave like charged rods, forming a highly viscous glassy state at higher concentration. Finally it is determined that similar selfassembly as in water is formed in methanol and dimethylformamide.