In Silico Study of Gold Nanoparticle Uptake into a Mammalian Cell: Interplay of Size, Shape, Surface Charge, and Aggregation

Abstract

The study of interactions between Au nanostructures and living cells is a fundamental aspect that can be applied for promising applications in nanomedicine. In the present work, we performed coarse-grained molecular dynamics (MD) simulations to observe the internalization pathways of Au nanostructures (nanospheres, nanocages, nanorods, nanoplates, and nanohexapods) into an idealized mammalian plasma membrane at an unprecedented level of complexity. Compared with a simple lipid bilayer model consisting of two lipid species, the different cellular uptake pathways of the gold nanoparticle (AuNP) were found. We highlight that the complexity of the lipid bilayer models plays an important role in the uptake pathway of nanoparticles (NPs). The permeability of aggregated AuNPs was much less than the NP counterpart. Spherical AuNPs showed pronounced size and surface charge dependence in their translocation through the plasma membrane. The translocation rates of different Au nanostructures were also evaluated, and we found that the Au nanohexapod exhibited highest cellular uptake. Understanding the interrelationship between size, shape, surface charge, and aggregation of Au nanostructures provides a clear view on the design of Au nanostructures for developing new diagnostic strategies and drug delivery.

Multinanoparticle Translocations in Phospholipid Membranes: Translocation Modes and Dynamic Processes

“…For example, the NPs with the ellipsoidal cross-section, e.g., the nanorods, cubes, nuts, and hexagonal columns, have different rates in the penetrating processes [39]. Furthermore, the simulation predicted that a sharp shape provides easy penetration, consistent with the experimental results [40]. The physicochemical properties, for example whether NPs carry electricity or not, also limit the penetration of the NPs [41−43].…”

Nanotheranostics against COVID-19: From multivalent to immune-targeted materials

“…Inverse computational fluid dynamics modeling enables identification of the contaminants and their spread including the coronavirus spread [ 226 ]. Regarding the COVID-19, coarse-grained molecular dynamics simulation enables evaluating the internalization of Au-based nanostructures into the mammalian cells and mechanism of targeting and delivery, and predicting the pharmacological profiles of NPs [ 217 , 227 ]. This might provide useful guidance towards the development of novel nanoformulations against SARS-CoV-2.…”

Molecular Modeling for Nanomaterial–Biology Interactions: Opportunities, Challenges, and Perspectives

“…The examples offered by the literature involve generic nanoparticles with different shapes or functionalization (Yang and Ma, 2010; Ding and Ma, 2012, 2014; Li and Hu, 2014; Li et al, 2014), gold nanoparticles (Lin et al, 2010; Rossi and Monticelli, 2016; Salassi et al, 2017; Lunnoo et al, 2019), and polymer systems (Schulz et al, 2012) such as dendrimers (Rossi and Monticelli, 2014, 2016), polystyrene (Rossi and Monticelli, 2016), and polyelectrolytes (Rossi and Monticelli, 2016).…”

“…Recently, Lunnoo et al (2019) employed the MARTINI CG model to simulate the cellular uptake of gold nanoparticles. Notably, they employed a more complex mammalian cell model previously proposed by Ingolfsson et al (2014), which includes 63 different lipid species asymmetrically distributed in the bilayer.…”