Microscopy techniques reveal hidden nanostructures in cells and tissues

Researchers at MIT have now developed a new way to overcome this limitation by making those "invisible" molecules visible

The approach builds on a widely used technique, extended microscopy, which was developed by the Massachusetts Institute of Technology, and should allow scientists to see molecular and cellular structures

"It's clear that the expansion process will reveal many new biological discoveries

Using this technique, Boyden and his colleagues demonstrated that they could image

Deblina Sarkar, assistant professor at the Media Lab and one of the study's lead authors, said: "Our technique, which we call extended disclosure, enables visualization of these previously hidden nanostructures, using hardware

The senior author of the study is Boyden; Lihui Cai, Director of the Picower Institute of Learning and Memory at MIT; and Thomas Brandpad

De-crowding

Imaging specific proteins or other molecules within cells needs to be labeled with fluorescent tags carried by the antibody, which bind

This is an obstacle to traditional imaging and one of the original expansion microscopes that Boyden first developed in 2015

To overcome this hurdle, researchers must find a way to make the tissue expand while maintaining the integrity

With so many markerable proteins, the researchers were able to identify tiny cellular structures within synapses, which are densely packed protein-filled connections between neurons

"This technique can be used to answer many biological questions about dysfunction of synaptic proteins, which are associated

New mode

The researchers also used their new technique to image β amyloid, a peptide

"In this paper, we don't speculate about what this biology might mean, but we're proving it exists

Sarkar says she's fascinated

Boyden and his team members are now collaborating with other labs to study cellular structures

"Time and time again, you're going to see really shocking things," he said

The researchers are also working to improve the technology so that they can image up to 20 proteins
at a time.
They are also working to adapt their process so that it can be used in human tissue samples
.

Sakar and her team, on the other hand, are developing miniature wirelessly powered nanoelectronic devices
that can be distributed in the brain.
They plan to integrate these devices with the extended display
.
"This could combine the intelligence of nanoelectronics with the nano-perspective technique of expansion technology to provide an integrated understanding of the function and structure of the brain," Sakar said
.

The study was conducted by the National Institutes of Health, the National Science Foundation, the Ludwig Family Foundation, the JPB Foundation, the Open Philanthropy Project, John Doerr, Lisa Yang and MIT's Tan-Yang Center for Autism Research, the U.
S.
Army Research Office, Charles Hieken, Tom Stocky, Kathleen Octavio, Lore McGovern, and Good Funded by
Ventures and HHMI.

Journal Reference:

1. Sarkar, D.
   , Kang, J.
   , Wassie, A.
   T.
   et al.
   .
   Revealing nanostructures in brain tissue via protein decrowding by iterative expansion microscopy.
   Nat.
   Biomed.
   Eng, 2022 DOI: 10.
   1038/s41551-022-00912-3