Secondary Structure-Encoded Control of Lipid Assembly by Radially Amphiphilic Peptides.

Area of Science:

• Biophysics
• Materials Science
• Supramolecular Chemistry

Background:

• Hierarchical superstructures of peptides and lipids are crucial for biological functions.
• Understanding the physical principles governing peptide-lipid self-assembly dynamics is essential.
• The role of peptide secondary structure in modulating these interactions is not fully understood.

Purpose of the Study:

• To investigate how secondary structure of radially amphiphilic peptides (RAPs) controls lipid assembly.
• To elucidate the physical principles governing the kinetics and thermodynamics of hierarchical superstructure formation.
• To provide theoretical guidance for designing peptide-lipid based hierarchical structures.

Main Methods:

• Free-energy landscape analysis of RAPs/POPG assembly.
• Kinetic pathway analysis comparing helical and non-helical RAPs.
• Thermodynamic barrier calculations for assembly transitions.

Main Results:

• RAP helicity promotes the formation of thermodynamically stable layer-by-layer superstructures.
• Two distinct assembly pathways were identified: singular-layer and layer-by-layer.
• Helical RAPs show a kinetic preference for the layer-by-layer pathway due to a lower enthalpic barrier.
• Increased peptide and lipid fluidity, driven by helical RAPs, facilitates escape from metastable states.

Conclusions:

• Peptide secondary structure, specifically helicity, is a key determinant in controlling lipid assembly pathways.
• The findings reveal a mechanism for achieving stable, defect-free hierarchical superstructures.
• This work offers valuable insights for the rational design of advanced peptide-lipid materials.