Peptide strand length controls the energetics of self-assembly and morphology of β-sheet fibrils.

Abstract

Self-assembling peptides can be used as versatile, natural, and multifunctional building blocks to produce a variety of well-defined nanostructures, materials and devices for applications in medicine and nanotechnology. Here, we concentrate on the 1D self-assembly of de novo designed Px-2 peptide β-strands into anti-parallel β-sheet tapes and higher order aggregates. We study six members of the Px-2 family, ranging from 3 amino acids (aa) to 13 aa in length, using a range of complementary experimental techniques, computer simulation and theoretical statistical mechanics. The critical concentration for self-assembly (c*) is found to increase systematically with decreasing peptide length. The shortest peptide found to self-assemble into soluble β-tapes in water is a 5 amino acid residue peptide. These investigations help decipher the role of the peptide length in controlling self-assembly, aggregate morphology, and material properties. By extracting free energies from these data using a statistical mechanical analysis and combining the results with computer simulations at the atomistic level, we can extract the entropy of association for individual β-strands.