Modulating peptide co-assembly via macromolecular crowding: Recipes for co-assembled structures

Area of Science:

• Biomaterials Science
• Computational Chemistry
• Supramolecular Chemistry

Background:

• Peptide-based biomaterials are vital for tissue engineering, wound healing, and drug delivery.
• Controlling peptide supramolecular structure and morphology is a significant challenge.
• Macromolecular crowding is a potential method to influence peptide assembly.

Purpose of the Study:

• To investigate the effect of hydrophobic crowders on the co-assembly of oppositely-charged synthetic peptides.
• To understand how crowder size and interactions dictate the final supramolecular architecture.
• To explore crowder-induced peptide assembly at low concentrations.

Main Methods:

• Discontinuous molecular dynamics simulations were employed.
• The PRIME20 force field was utilized for simulations.
• Systems included mixtures of CATCH(6K+) and CATCH(6E-) peptides with varying crowder sizes (10-80 Å) and interaction types (hard-sphere, square-well/shoulder).

Main Results:

• Crowders acted as chaperones, inducing co-assembly at low peptide concentrations.
• Small hard-sphere crowders promoted multilayer fibril formation.
• Large, hydrophobic crowders favored monolayer β-sheet structures and inhibited fibril formation.

Conclusions:

• Crowder size and sidechain interaction strength are key determinants of peptide co-assembly architecture.
• This study demonstrates a method to control peptide supramolecular structures using macromolecular crowding.
• Findings have implications for designing advanced peptide-based biomaterials.