Interaction of Graphitic Carbon Nitride with Cell Membranes: Probing Phospholipid Extraction and Lipid Bilayer Destruction.
Yiping FengJiayong LaoJiale ZouZhiyu ZhuDaguang LiGuoguang LiuLiang MaoPublished in: Environmental science & technology (2022)
Understanding how nanomaterials interact with cell membranes has important implications for ecotoxicology and human health. Here, we investigated the interactions between graphitic carbon nitride (g-C 3 N 4 , CN) and red blood cells, a plausible contact target for nanoparticles when they enter the bloodstream. Through a hemolysis assay, the cytotoxicity of CN derived from different precursors was quantitatively assessed, which is highly related to the surface area of CN. Reactive oxygen species (ROS) generation and lipid peroxidation detection confirmed that CN causes rapid cell membrane rupture by a physical interaction mechanism rather than ROS-related chemical oxidation. Dye leakage assay and theoretical simulation indicated that the less-layered CN is prone to folding inward to wrap and extract lipid molecules from cell membranes. The electron-rich inherent pores of CN play a dominant role in capturing the headgroups of phospholipids, whereas the hydrophobic interaction is critical for the anchoring of lipid tails. Our further experimental evidence demonstrated that the destructive extraction of phospholipids from cell membranes by CN occurs primarily in the outer leaflet, and phosphatidylcholine is the most easily extracted lipid. Moreover, the formation of protein corona on CN was found to decrease the nonspecific interactions but increase steric repulsion, thus mitigating CN cytotoxicity. Overall, our data provide a molecular basis for CN's cytotoxicity.
Keyphrases
- lymph node metastasis
- fatty acid
- single cell
- reactive oxygen species
- human health
- cell therapy
- squamous cell carcinoma
- high throughput
- red blood cell
- dna damage
- cell death
- physical activity
- stem cells
- oxidative stress
- escherichia coli
- quantum dots
- small molecule
- climate change
- left ventricular
- mental health
- heart failure
- machine learning
- bone marrow
- hydrogen peroxide
- atrial fibrillation
- single molecule
- gram negative
- drug induced
- sensitive detection