Lipid Membrane-Selective Interactions Driven by Nanosilver Anisotropy: Insights from Prokaryotic and Erythrocyte Models

Abstract

The increasing use of silver nanoparticles (AgNPs) 6 in medical applications highlights the need for thorough studies of 7 their health effects, particularly at the cellular level. Due to the 8 complexity of replicating real cell membranes, Langmuir mono9 layers (LMs) are employed as simplified models of the initial 10 biological barrier. These systems allow for controlled conditions to 11 investigate molecular behavior at the membrane interface, offering 12 insights into the fundamental mechanisms involved. In this 13 research, we explore the effects of the shape and electronic 14 anisotropy of AgNPs on bacterial and erythrocyte membrane 15 models using dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol (CHOL) combinations. The interaction between the 16 lipids and silver nanoparticles was investigated using film balance measurements by analyzing surface pressure (π−A) and membrane 17 potential (ΔV−A) isotherms. These measurements were complemented by X-ray reflectometry to obtain detailed structural 18 information at the interface. Additionally, in vitro experiments were conducted to provide a behavioral profile of the nanoparticles’ 19 effects, linking physicochemical interactions with cellular responses. Our findings demonstrate that the shape anisotropy of prism-like 20 silver nanoparticles (p-AgNPs) significantly impacts membrane structural integrity and mechanical properties, with the extent of 21 these effects depending on membrane composition and cholesterol content. Prism-like silver nanoparticles interact more strongly 22 with DPPC monolayers than spherical nanoparticles (s-AgNPs), inducing higher surface pressure and a decrease in membrane 23 rigidity due to lipid extraction. In DPPC/CHOL monolayers, p-AgNPs promote CHOL microdomain formation and disrupt DPPC 24 organization, with these effects becoming more pronounced at higher CHOL concentrations. Prism-like nanosilver also enhances 25 lipid extraction and membrane permeability in bacterial-like membranes, while in erythrocyte-mimetic membranes, it disrupts 26 membrane organization and reduces rigidity, with cholesterol modulating this impact. These results suggest that p-AgNPs exhibit 27 potent antibacterial properties but also pose risks of destabilizing eukaryotic cell membranes. Overall, the study explores the 28 concentration-dependent antibacterial and cytotoxic effects of p-AgNPs, highlighting how their morphological anisotropy plays a 29 decisive role in modulating nanoparticle/membrane interactions. By uncovering specific mechanisms at the bionano interface, this 30 work sets an important precedent for the rational design of nanosilver-based devices and treatments, contributing valuable 31 knowledge to the safe and effective application of anisotropic nanomaterials in biomedicine.