title: Single-Cell Mechanics Provides an Effective Means To Probe in Vivo Interactions between Alveolar Macrophages and Silver Nanoparticles.
abstract: Single-cell mechanics, derived from atomic force microscopy-based technology, provides a new and effective means to investigate nanomaterial-cell interactions upon in vivo exposure. Lung macrophages represent initial and important responses upon introducing nanoparticles into the respiratory tract, as well as particle clearance with time. Cellular mechanics has previously proven effective to probe in vitro nanomaterial-cell interactions. This study extends technology further to probe the interactions between primary alveolar macrophages (AM) and silver nanoparticles (AgNPs) upon in vivo exposure. Two types of AgNPs, 20 and 110 nm, were instilled to rat lung at 0.5 mg AgNPs/kg body weight, and allowed 24 h interaction. The consequences of these interactions were investigated by harvesting the primary AMs while maintaining their biological status. Cellular mechanics measurements revealed the diverse responses among AM cells, due to variations in AgNP uptake and oxidative dissolving into Ag(+). Three major responses are evident: zero to low uptake that does not alter cellular mechanics, intracellular accumulation of AgNPs trigger cytoskeleton rearrangement resulting in the stiffening of mechanics, and damage of cytoskeleton that softens the mechanical profile. These effects were confirmed using confocal imaging of F-actin and measurements of reactive oxygen species production. More detailed intracellular interactions will also be discussed on the basis of this study in conjunction with prior knowledge of AgNP toxicity.
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Ying X
authors.initials: YX
authors.lastname: Liu
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Arpad
authors.initials: A
authors.lastname: Karsai
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Anderson
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Silva
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Uyeminami
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.affiliation: Department of Chemistry, ‡Center for Health and the Environment, §Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and ∥Department of Pediatrics, School of Medicine, University of California , Davis, California 95616, United States.
authors.forename: Gang-yu
authors.initials: GY
authors.lastname: Liu
mesh_terms: D000818:Animals; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D015335:Molecular Probes; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry*; D059010:Single-Cell Analysis
chemical_list: D015335:Molecular Probes; D017382:Reactive Oxygen Species; D012834:Silver