Peptide-Ligand Cooperative Interplay Drives Gold Nanoparticle Encapsulation by Protein Cages

Area of Science:

• Biophysics
• Synthetic Biology
• Nanotechnology

Background:

• Encapsulation is key for synthetic biology, biocatalysis, and drug delivery.
• Controlling cargo loading into protein cages like encapsulins is a significant challenge.

Purpose of the Study:

• To achieve a molecular-level understanding of gold nanoparticle encapsulation within encapsulin protein cages.
• To investigate the influence of salt concentration, nanoparticle functionalization, and peptides on encapsulation efficiency.

Main Methods:

• Experimental studies examining salt concentration, ligand functionalization, and peptide effects.
• Molecular dynamics simulations to analyze the free-energy landscape of nanoparticle-protomer interactions.

Main Results:

• Identified three distinct salt-dependent binding regimes: strong nanoparticle-protomer binding at low salt, intermediate binding, and weak attraction at high salt.
• Demonstrated that cooperative effects between ligands and peptides enhance encapsulation robustness against salt variations.
• Ligands mediate electrostatic attraction and peptide extension, while peptides broaden recruitment and prevent kinetic trapping.

Conclusions:

• The study provides molecular insights into encapsulation energetics and peptide-ligand cooperation.
• Findings guide the rational design of bio-inspired nanocages for targeted delivery and synthesis applications.