Reprinted with permission from ACS Nano2019, 13, 8, 8680-8693. Copyright 2019 American Chemical Society.
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.
Liming Wang,1 Peiyu Quan,1,2 Serena H. Chen,4 Wei Bu,3 Yu-Feng Li,1 Xiaochun Wu,5 Junguang Wu,1,2 Leili Zhang,4 Yuliang Zhao,1 Xiaoming Jiang,1 Binhua Lin,3 Ruhong Zhou,4,6 and Chunying Chen1
1CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100049, China
2University of Chinese Academy of Sciences, Beijing 100049, China
3NSF’s ChemMatCARS and Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States
4IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States
5CAS Key Laboratory of Standardization and Measurement for Nanotechnology and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology, Beijing 100190, China
6Department of Chemistry, Columbia University, New York, New York 10027, United States
ACS Nano2019, 13, 8, 8680-8693
DOI: 10.1021/acsnano.9b00114