Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 41, Pages E4289-E4297Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1409321111
Keywords
dynamic light scattering; plasmon resonance; nanoparticle diffusion; diffusion in mucus; diffusion in extracellular matrix
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Funding
- National Institutes of Health [R21HL111968, R21CA179204]
- pilot funds
- Carolina Center of Cancer Nanotechnology Excellence [U54CA119343]
- National Science Foundation [DMR-1056653, DMS-110281]
- Cystic Fibrosis Foundation [BUTTON07XX0]
- [U01ES019472]
- [P01HL108808]
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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 (D-T) 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, D-T of GNRs decreases with both increasing collagen concentration and cell density. Similarly, D-T 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.
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