Factors governing the self-assembly of a β-hairpin peptide at the air-water interface

Peptide 1 is a 14-residue peptide designed to form an amphiphilic beta-hairpin. It was found previously that 1 self-assembles at the air-water interface to form two-dimensionally crystalline domains that persist for hundreds of nanometers. Peptide 1 has several structural features that could enhance or impede its ability to self-assemble, including six glutamic acid residues (which, if ionized, could cause electrostatic repulsions), an aromatic fluorophore, and a dPro-Gly type II' beta-turn (which could each be involved in van der Waals interactions). We have found that the glutamic acid residues in the monolayers are not ionized on distilled water subphases even though they would be expected to be given their pK(a)s. Thus, under these conditions, they do not inhibit the self-assembly of 1. However, on higher pH subphases they can completely destabilize monolayers of 1. Both the fluorophore and the dPro-Gly turn were found by comparison to analogous peptides that lacked these structural features to enhance self-assembly of 1. These enhancements were quantified by fitting surface pressure-molecular area isotherms to an equation of state.