GoKawiilHigh-resolution images can be produced by increasing the size of a nerve cell before fluorescence-microscopy imaging.Credit: Arthur Chien/SPL
A technique that supersizes cells to reveal minute details has gone big — really big.
Using a polymer similar to those used in nappies to make them super-absorbent, scientists have expanded the volume of biological samples so they are one billion times bigger — 1,000-fold larger in each dimension. This level of expansion could inflate an individual cell to the size of a mouse brain and a US-dime-sized sample to the proportion of an Olympic swimming pool.
Researchers have used the technique to map the positions of amino acids (the building blocks of proteins) in proteins and small molecules called peptides using conventional light microscopes. The approach is outlined in a preprint posted on bioRxiv earlier this month1.
Previously, viewing molecules in such fine detail has typically been achieved by using costly and complicated techniques such as cryogenic electron microscopy (cryo-EM) and X-ray crystallography. “This is the democratization of structural biology,” says study co-author Silvio Rizzoli, a neuroscientist and imaging specialist at the University Medical Center Göttingen (UMG) in Germany.
“It’s really getting down to a ground-truth description of what a protein is,” adds co-author Helena Hu, a bioengineer at the Massachusetts Institute of Technology (MIT) in Cambridge.
Expansion microscopy
The laws of physics limit the optical power of light microscopes: objects that are less than about 200 nanometres apart cannot be distinguished. ‘Super-resolution’ light-microscopy techniques, which usually rely on optical tricks and costly kit, have cut this resolution limit to below 10 nm.
In 2015, MIT neuroengineer Edward Boyden, a co-author of the study, and his colleagues invented an alternative way to get extremely high resolution using ordinary fluorescent light microscopes2. Using a swelling hydrogel, the researchers expanded tissue samples about fourfold in each direction. This moved cellular components away from one another, improving resolution.
Researchers have since adapted Boyden’s ‘expansion microscopy’ method to swell samples to greater volumes, but inflation has generally been limited to about a 20-fold increase in size.
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