You need an expensive super-resolution microscope in your lab but can’t afford it. Now what? A new technique allows scientists to image nanoscale structures inside cells without using the traditional high-end microscope.
MIT researchers have developed a way to expand tissue before imaging it and, in the process, achieve nanoscale resolution with a conventional light microscope. They successfully expanded tissue 20-fold in one step. At that resolution, approximately 20 nanometers, scientists can view organelles inside cells and clusters of proteins. This allows them to see cell structures like microtubules and mitochondria, as well as clusters of proteins. The study will appear in Nature Methods.
According to Laura Kiessling, Novartis Professor of Chemistry at MIT and a member of the Broad Institute of MIT and Harvard and MIT’s Koch Institute for Integrative Cancer Research, “What this new technique allows you to do is see things that you couldn’t normally see with standard microscopes. It drives down the cost of imaging because you can see nanoscale things without the need for a specialized facility.”
The initial version of the new technique expanded tissue fourfold, allowing researchers to obtain images with a resolution of approximately 70 nanometers. In 2017, Boyden’s lab modified the process to include a second expansion step, achieving an overall 20-fold expansion. The new study performs 20-fold expansion with only a single step, using a gel that was highly absorbent and mechanically stable so that it wouldn’t fall apart when expanded.
The technique enables the imaging of many tiny structures within brain cells, including structures called synaptic nanocolumns. The researchers also imaged microtubules — hollow tubes that help give cells their structure and play essential roles in cell division. They were also able to see mitochondria and even the organization of individual nuclear pore complexes. They are now using the technique to image carbohydrates known as glycans, found on cell surfaces and help control cells’ interactions with their environment. Scientists can also use this method to image tumor cells, allowing them to see how proteins are organized within those cells much more easily than previously possible.
