title: Probing biological nanotopology via diffusion of weakly constrained plasmonic nanorods with optical coherence tomography.
abstract: Biological materials exhibit complex nanotopology, i.e., a composite liquid and solid phase structure that is heterogeneous on the nanoscale. The diffusion of nanoparticles in nanotopological environments can elucidate biophysical changes associated with pathogenesis and disease progression. However, there is a lack of methods that characterize nanoprobe diffusion and translate easily to in vivo studies. Here, we demonstrate a method based on optical coherence tomography (OCT) to depth-resolve diffusion of plasmon-resonant gold nanorods (GNRs) that are weakly constrained by the biological tissue. By using GNRs that are on the size scale of the polymeric mesh, their Brownian motion is minimally hindered by intermittent collisions with local macromolecules. OCT depth-resolves the particle-averaged translational diffusion coefficient (DT) of GNRs within each coherence volume, which is separable from the nonequilibrium motile activities of cells based on the unique polarized light-scattering properties of GNRs. We show how this enables minimally invasive imaging and monitoring of nanotopological changes in a variety of biological models, including extracellular matrix (ECM) remodeling as relevant to carcinogenesis, and dehydration of pulmonary mucus as relevant to cystic fibrosis. In 3D ECM models, DT of GNRs decreases with both increasing collagen concentration and cell density. Similarly, DT of GNRs is sensitive to human bronchial-epithelial mucus concentration over a physiologically relevant range. This novel method comprises a broad-based platform for studying heterogeneous nanotopology, as distinct from bulk viscoelasticity, in biological milieu.
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255;
authors.forename: Raghav K
authors.initials: RK
authors.lastname: Chhetri
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255;
authors.forename: Richard L
authors.initials: RL
authors.lastname: Blackmon
authors.affiliation: Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695;
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Wu
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255; Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248;
authors.forename: David B
authors.initials: DB
authors.lastname: Hill
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248;
authors.forename: Brian
authors.initials: B
authors.lastname: Button
authors.affiliation: Lineberger Comprehensive Cancer Center/Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295; and.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casbas-Hernandez
authors.affiliation: Lineberger Comprehensive Cancer Center/Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295; and.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
authors.affiliation: Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695;
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Tracy
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7513 aold@physics.unc.edu.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Oldenburg
mesh_terms: D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004058:Diffusion; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009093:Mucus / Q000187:drug effects; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D012996:Solutions; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D041623:Tomography, Optical Coherence
chemical_list: D012996:Solutions; D011092:Polyethylene Glycols; D006046:Gold; D003094:Collagen
keywords: diffusion in extracellular matrix; diffusion in mucus; dynamic light scattering; nanoparticle diffusion; plasmon resonance