Stability of Ligands on Nanoparticles Regulating the Integrity of Biological Membranes at the Nano–Lipid Interface

Abstract

When nanoparticles interact with cellular or organelle membranes, the coating ligands are known to affect the integrity of the membranes, which regulate cell death and inflammation. However, the molecular mechanisms of this modulation remain unresolved. Here, we use synchrotron X-ray liquid surface scattering and molecular dynamics simulations to study interface structures between phospholipids and gold nanorods (AuNRs) coated by surfactant and polyelectrolyte. These ligands are two types of widely used surface modification with different self-assembled structures and stabilities on the surface of nanoparticles. We reveal distinct mechanisms of the ligand stability in disrupting membrane integrity. We find that the cationic surfactant ligand cetyltrimethylammonium bromide detaches from the AuNRs and inserts into phospholipids, resulting in reduced membrane thickness by compressing the phospholipids to align with the shorter ligand. Conversely, the cationic polyelectrolyte ligand poly­(diallyldimethylammonium chloride) is more stable on AuNRs; although it adsorbs onto the membrane, it does not cause much impairment. The distinct coating ligand interactions with phospholipids are further verified by cellular responses including impaired lysosomal membranes and triggered inflammatory effects in macrophages. Together, the quantitative analysis of interface structures elucidates key bio–nano interactions and highlights the importance of surface ligand stability for safety and rational design of nanoparticles.

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

“…Occurrence of positively charged fragments in amphiphilic scaffold is responsible for their attractiveness in nanotechnological applications as antimicrobial and bioimaging agents [5,6], corrosion inhibitors [7], supramolecular catalysts [8], stabilizers of nanoparticles and nanocarriers [9,10], and, especially as, drug and gene nanocarriers [11]. Cationic head groups of surfactants provide their high affinity toward biopolyanions, such as DNA [12,13], cell membranes, and intracellular organelles, such as mitochondrion, thereby initiating the development of perspective field of therapy, the so-called mitochondrion medicine [14,15].…”

Molecular Mechanisms, Characterization Methods, and Utilities of Nanoparticle Biotransformation in Nanosafety Assessments

“…By integrating SR-TXM and in situ SR-X-ray absorption near edge structure (SR-XANES) spectrometry, researchers in Beijing Synchrotron Radiation Facility successfully identified the chemical transformation of silver NPs in single human monocyte cell. [186] Qu et al employed microbeam synchrotron radiation X-ray fluorescence (µ-SRXRF) and microbeam XANES technique to decipher the composition changes of NPs in the metabolic process of Caenorhabditis elegans. [187] Mei et al investigated the translocation, precise degraded species/ratios of polyvinylpyrrolidone-modified 2H-phase MoS 2 nanosheets in normal human umbilical vein endothelial and hepatoma cells.…”

Biological Behavior Regulation of Gold Nanoparticles via the Protein Corona

“…The cell membrane plays a key role in the uptake of NPs. The properties of coating ligands on the surface of NPs are known to affect the integrity of the membranes, [ 60 ] which may regulate cell state, trigger inflammation, and causes cell death. [ 61 ] Thus, investigating the underlying mechanisms of the NP‐cell membrane interface is a key entry point for understanding nano‐safety issues.…”

“…A recent work has reported that GNRs protected by CTAB may rupture the cell membrane, causing cytotoxicity and inflammatory responses, due to the positive charge of CTAB. [ 60 ] Once the proteins (such as FBS) are bound to the surface of CTAB‐GNRs, the toxic surface is shielded by the PC. [ 56 ] After phagocytosis, the FBS on the surface of CTAB‐GNRs was hydrolyzed in the presence of various hydrolases in the lysosome.…”