title: New approach to investigate the cytotoxicity of nanomaterials using single cell mechanics.
abstract: Current in vitro methods to assess nanomaterial cytotoxicity involve various assays to monitor specific cellular dysfunction, such as metabolic imbalance or inflammation. Although high throughput, fast, and animal-free, these in vitro methods suffer from unreliability and lack of relevance to in vivo situations. New approaches, especially with the potential to reliably relate to in vivo studies directly, are in critical need. This work introduces a new approach, single cell mechanics, derived from atomic force microscopy-based single cell compression. The single cell based approach is intrinsically advantageous in terms of being able to directly correlate to in vivo investigations. Its reliability and potential to measure cytotoxicity is evaluated using known systems: zinc oxide (ZnO) and silicon dioxide (SiO2) nanoparticles (NP) on human aortic endothelial cells (HAECs). This investigation clearly indicates the reliability of single cell compression. For example, ZnO NPs cause significant changes in force vs relative deformation profiles, whereas SiO2 NPs do not. New insights into NPs-cell interactions pertaining to cytotoxicity are also revealed from this single cell mechanics approach, in addition to a qualitative cytotoxicity conclusion. The advantages and disadvantages of this approach are also compared with conventional cytotoxicity assays.
authors.affiliation: Department of Chemistry, University of California, Davis , One Shields Avenue, Davis, California 95616, United States.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Zimmer
authors.forename: Ying X
authors.initials: YX
authors.lastname: Liu
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Morgan
authors.forename: Guohua
authors.initials: G
authors.lastname: Yang
authors.forename: Kang-Hsin
authors.initials: KH
authors.lastname: Wang
authors.forename: Ian M
authors.initials: IM
authors.lastname: Kennedy
authors.forename: Abdul I
authors.initials: AI
authors.lastname: Barakat
authors.forename: Gang-yu
authors.initials: GY
authors.lastname: Liu
mesh_terms: D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D055119:Elastic Modulus; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018625:Microscopy, Atomic Force; D012822:Silicon Dioxide / Q000737:chemistry; D059010:Single-Cell Analysis; D015034:Zinc Oxide / Q000737:chemistry
chemical_list: D012822:Silicon Dioxide; D015034:Zinc Oxide