Atomistic Simulations on Interactions between Amphiphilic Janus Nanoparticles and Lipid Bilayers: Effects of Lipid Ordering and Leaflet Asymmetry

Abstract

Amphiphilic Janus nanoparticles, which are hydrophilic on one-half of the particle surface and hydrophobic on the other half, are ideal carrier candidates for drug delivery due to their unique physicochemical properties. In this study, we investigate the interactions between amphiphilic Janus nanoparticles coated with hydrophilic and hydrophobic ligands on each half of the surface of the nanoparticle and lipid bilayers with either symmetric or asymmetric leaflet structure and in different phases using atomistic molecular dynamics simulations. The results show that the Janus nanoparticle can easily insert into the liquid-disordered lipid bilayer and asymmetric lipid bilayers with the hydrophobic ligands inserted into the liquid-ordered leaflet. However, the nanoparticle barely inserts into the symmetric liquid-ordered lipid bilayer and tends to be adsorbed onto the surface of the liquid-ordered bilayers with the hydrophilic ligands contacting the surface of the bilayer. The insertion of the nanoparticle is mainly dominated by the hydrophobicity of the ligands, the lipid ordering, and the curvature of the bilayer. Rotation of the nanoparticle only occurs during the initial adsorption process of the nanoparticle onto the surface of the lipid bilayers. This work provides new insight into understanding the interactions of amphiphilic Janus nanoparticles with model biological membranes at the atomistic scale and the application of Janus nanoparticles for drug delivery.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Antiseptic Picloxydine, Octenidine, Miramistin [470], Polyhexamethylene Biguanide [471] Insecticide Parathione [132], Fipronil [472], Dibutyl succinate [203] Former Drugs d-sotalol, cisapride [473], piracetam (status varies among countries) [474], ORG-12962 [199] Toxic xenobiotic Polybrominated-diphenyl-ethers [475], Bisphenol [476], Perfluoroalkyls [477], nitroaromatic explosives (TNT,2A, and 24DA) [478][479][480][481], 1,4-Dioxane [482], Benzo[a]pyrene [483] Nanomaterials Graphene [484][485][486][487], Carbon Dots [488], Phosphorene Oxide Nanosheets [489], Gold Nanoparticles [490][491][492], Titanium Dioxide Nanoparticles [493], Generic Nanoparticles (coarse grained) [494], Fullerene [495][496][497][498], Previous reviews [499] Polymers Poly(ethyleneoxide)-Poly-(propylene oxide) [500], polyethylenimine [501], Poloxamer [502,503], Pluronics [504,505], poly(ethyleneglycol)-desferrioxamine/ gallium [506], PEG functionalized with carbochydrates [507] and peptides…”

Engineering macrophage targeted punicalagin nanoparticles by computational modeling to alleviate methotrexate induced neutropenia

“…24 Qu et al 2020 described the atomistic simulations between nanoparticles and lipid bilayers. 25 Stillman et al 2020 describe numerous methods of in-silico modeling for cancer nanomedicines. 26 Similarly Casalin et al, 2019 described molecular modeling for nanomaterials, their challenges and their perspectives are also discussed in detail.…”

Engineering of macrophage targeted Punicalagin nanoparticles by computational modeling to alleviate methotrexate induced neutropenia

“…Recently in this pandemic era, Weiss et al, 2020 reviewed the nanotechnology-based approaches against COVID-19 pandemic [24]. Qu et al 2020 described the atomistic simulations between nanoparticles and lipid bilayers [25]. Stillman et al 2020 describe numerous methods of in-silico modeling for cancer nanomedicines [26].…”