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Probing IgG1 FC-Multimodal Nanoparticle Interactions: A Combined Nuclear Magnetic Resonance and Molecular Dynamics
Ronak B Gudhka, Mayank Vats, Camille L Bilodeau
1Mass Spectrometry & Biophysics, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Langmuir : the ACS Journal of Surfaces and Colloids
|October 11, 2021
Summary
This study used NMR and simulations to show how IgG1 Fc fragments bind to nanoparticle surfaces. Binding affinity increased significantly on nanoparticles compared to free ligands, revealing distinct binding modes for different ligands.
Area of Science:
- Biophysics
- Structural Biology
- Nanotechnology
Background:
- Understanding the binding of therapeutic proteins like IgG1 Fc to surfaces is crucial for drug delivery and biomaterial design.
- Multimodal surfaces offer unique binding properties compared to simple ligands.
Purpose of the Study:
- To investigate the binding interactions of IgG1 Fc with functionalized gold nanoparticles using NMR and molecular dynamics simulations.
- To elucidate the role of ligand density and salt concentration on Fc binding affinity and mode.
Main Methods:
- Solution-phase NMR spectroscopy with perdeuterated, 15N-labeled IgG1 Fc.
- Synthesis of gold nanoparticles functionalized with cation-exchange ligands (Capto and Nuvia).
- Molecular dynamics simulations to complement experimental findings.
Main Results:
- Micromolar binding affinities of Fc to nanoparticle-bound ligands, significantly higher than millimolar affinities in solution.
- Distinct binding modes observed: focused hydrophobic interaction for Capto, diffuse electrostatic interaction for Nuvia.
- Decreased binding affinity with lower ligand density and increased salt concentration, with salt inducing a shift in Nuvia binding mode.
Conclusions:
- Multimodal nanoparticle surfaces enhance Fc binding affinity through cooperativity and avidity effects.
- Ligand density and salt concentration modulate Fc binding interactions, influencing the specific binding regions.
- The combined biophysical and simulation approach provides molecular insights into Fc-surface interactions for biotherapeutic applications.
