A series of amphiphilic lipopeptides, ALPs, consisting of an alternating hydrophilic and hydrophobic amino acid residue sequence coupled to a phospholipid tail, was designed to form supramolecular assemblies composed of beta-sheet monolayers decorated by lipid tails at the air-water interface. A straightforward synthetic approach based on solid-phase synthesis, followed by an efficient purification protocol was used to prepare the lipid-peptide conjugates. Structural insight into the organization of monolayers was provided by surface pressure versus area isotherms, circular dichroism, Fourier transform infrared spectroscopy, and Brewster angle microscopy. In situ grazing-incidence X-ray diffraction (GIXD) revealed that lipopeptides six to eight amino acids in length form a new type of 2D self-organized monolayers that exhibit beta-sheet ribbons segregated by lipid tails. The conclusions drawn from the experimental findings were supported by a representative model based on molecular dynamics simulations of amphiphilic lipopeptides at the vacuum-water interface.

Grazing incidence X-ray diffraction measurements were performed on monolayer films of three amphiphilic and acidic β-sheet peptides having the general sequence Pro-Y-(Z-Y)(5)-Pro, with Y = Asp or Glu and Z = Phe or Leu denoted, P(FD)-5, P(LE)-5, P(LD)-5, and the 1:1 molar ratio mixture of P(LD)-5 and P(LE)-5. The crystalline domains of these peptides exhibited compressibility and elasticity of the crystalline unit cell indicated by changes in diffraction patterns on compression. Higher compressibility values appeared to be associated with more favorable cross-strand interactions between peptides with the larger side chains, whereas P(LD)-5, decorated by the smaller side chain amino acids, exhibited the lowest crystalline compressibility. Diffraction patterns provided evidence for a new subunit cell generated by the pleated β-strand motif in an apparently favorable mode of cross-strand intermolecular packing in β-sheets. The study contributes to the understanding of β-sheet flexibility at interfaces with relevance to natural proteins and designed biomaterials composed of β-sheet peptides.