NIH: Light microscopy has been a mainstay of neuroscience and many areas
of biology for more than a century. But the resolution limit of light,
based on immutable physical principles, has kept the fine details of
many structures out of view. Scientists can’t change the laws of
physics—but NIH-supported researchers recently devised a highly creative
way to see images that were previously out of reach, by expanding the
contents of tissue sections up to five times their normal size, while
maintaining the anatomic arrangements. The new approach takes advantage
of a compound used in—get this—disposable diapers!
By harnessing the super-absorbent properties of sodium polyacrylate, a
polymer commonly used in diapers, a team from the Massachusetts
Institute of Technology (MIT) developed a new technique that makes it
possible for conventional microscopes to produce super high-resolution
images of brain cells. The name of the new technique? Expansion
microscopy.
To create such images, MIT neuroscientist
Ed Boyden, along with graduate students Fei Chen and Paul Tillberg,
start by labeling proteins of interest with fluorescent antibodies. The
sample is then embedded within a 3D mesh of sodium polyacrylate, with
the fluorescent molecules on the antibodies connecting to the sodium
polyacrylate. The proteins are dissolved, leaving the fluorescent labels
attached to the expandable polymer. The researchers then add water, and
the polymer matrix swells evenly in three dimensions just as it does in
a diaper. The final product is a neural landscape with greatly enlarged
cell structures that also appear transparent, making them perfect for
microscopy.
Expansion microscopy can be used to scan whole brain structures and
show entire neural networks in 3D. To date, Boyden, who is a recipient
of both the NIH Director’s Pioneer and Transformative Research awards,
has tested expansion microscopy on brain cells cultured in the lab and
on slices of neural tissue from mice. Who knows where he’ll take it from
here?