Amphiphilic Nanoparticles as Biomimetic Transport Proteins

Mukarram Tahir, Massachusetts Institute of Technology

Proteins such as serum albumin facilitate the transport of hydrophobic small molecules, such as fatty acids and lipophilic drugs in biological systems. These proteins typically expose hydrophobic crevices that allow non-covalent encapsulation of small molecules for eventual delivery to cellular targets. Recent experiments have demonstrated that gold nanoparticles functionalized with an amphiphilic surface monolayer can similarly encapsulate hydrophobic molecules and deliver them across lipid membranes. In this work, we use molecular dynamics simulations to provide an atomic-resolution understanding of this encapsulation and release process. In particular, we use a combination of unbiased simulations and free-energy analysis to characterize the propensity and dynamics of small molecular incorporation into a nanoparticle's surface monolayer and characterize the resulting impact on nanoparticle morphology. We also investigate the thermodynamics and kinetics of the pathway through which nanoparticles can ultimately deliver encapsulated small molecules to a lipid membrane target. The ability to design nanoparticles that bind hydrophobic small molecules in this manner points to the possibility of engineering synthetic nanostructures that can function as biomimetic transport proteins and solubilize hydrophobic molecules in the aqueous environment of biological systems.

Abstract Author(s): Mukarram A. Tahir, Alfredo Alexander-Katz