Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain
Nature Nanotech. 2016-11-21; 12(3): 238-243
DOI: 10.1038/nnano.2016.248
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The brain is a dynamic structure with the extracellular space (ECS) taking up
almost a quarter of its volume. Signalling molecules, neurotransmitters and
nutrients transit via the ECS, which constitutes a key microenvironment for
cellular communication and the clearance of toxic metabolites. The spatial
organization of the ECS varies during sleep, development and aging and is
probably altered in neuropsychiatric and degenerative diseases, as inferred from
electron microscopy and macroscopic biophysical investigations. Here we show an
approach to directly observe the local ECS structures and rheology in brain
tissue using super-resolution imaging. We inject single-walled carbon nanotubes
into rat cerebroventricles and follow the near-infrared emission of individual
nanotubes as they diffuse inside the ECS for tens of minutes in acute slices.
Because of the interplay between the nanotube geometry and the ECS local
environment, we can extract information about the dimensions and local viscosity
of the ECS. We find a striking diversity of ECS dimensions down to 40 nm, and as
well as of local viscosity values. Moreover, by chemically altering the
extracellular matrix of the brains of live animals before nanotube injection, we
reveal that the rheological properties of the ECS are affected, but these
alterations are local and inhomogeneous at the nanoscale.