Nano Research

Article Title

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures


amphiphilic designer peptides, lipids, nanostructures, lamellae, small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM)


ABSTRACT Lipids exhibit an extraordinary polymorphism in self-assembled mesophases, with lamellar phases as the most relevant biological representative. To mimic lipid lamellar phases with amphiphilic designer peptides, seven systematically varied short peptides were engineered. Indeed, four peptide candidates (V4D, V4WD, V4WD2, I4WD2) readily self-assembled into lamellae in aqueous solution. Small-angle X-ray scattering (SAXS) patterns revealed ordered lamellar structures with a repeat distance of ~4–5 nm. Transmission electron microscopy (TEM) images confirmed the presence of stacked sheets. Two derivatives (V3D and V4D2) remained as loose aggregates dispersed in solution; one peptide (L4WD2) formed twisted tapes with internal lamellae and an antiparallel β-type monomer alignment. To understand the interaction of peptides with lipids, they were mixed with phosphatidylcholines. Low peptide concentrations (1.1 mM) induced the formation of a heterogeneous mixture of vesicular structures. Large multilamellar vesicles (MLV, d-spacing ~6.3 nm) coexisted with oligo- or unilamellar vesicles (~50 nm in diameter) and bicelle-like structures (~45 nm length, ~18 nm width). High peptide concentrations (11 mM) led to unilamellar vesicles (ULV, diameter ~260–280 nm) with a homogeneous mixing of lipids and peptides. SAXS revealed the temperature-dependent fine structure of these ULVs. At 25 °C the bilayer is in a fully interdigitated state (headgroup-to-headgroup distance dHH ~ 2.9 nm), whereas at 50 °C this interdigitation opens up (dHH ~ 3.6 nm). Our results highlight the versatility of self-assembled peptide superstructures. Subtle changes in the amino acid composition are key design elements in creating peptide- or lipidpeptide nanostructures with richness in morphology similar to that of naturally occurring lipids.

Graphical Abstract


Tsinghua University Press