To understand a brain, watch all of it.

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via MIT News

April 23, 2025

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Edward Boyden

Professor of Media Arts and Sciences; Y. Eva Tan Professor in Neurotechnology

Fei Chen

Former Research Assistant

Paul Tillberg

Former Postdoctoral Associate

Projects

Tools for mapping the molecular architecture and wiring of the brain

By Jennifer Michalowski

Nearly 150 years ago, scientists began to imagine how information might flow through the brain based on the shapes of neurons they had seen under the microscopes of the time. With today’s imaging technologies, scientists can zoom in much further, seeing the tiny synapses through which neurons communicate with one another, and even the molecules the cells use to relay their messages. These inside views can spark new ideas about how healthy brains work and reveal important changes that contribute to disease.

This sharper view of biology is not just about the advances that have made microscopes more powerful than ever before. Using methodology developed in the lab of MIT McGovern Institute for Brain Research investigator Edward Boyden , researchers around the world are imaging samples that have been swollen to as much as 20 times their original size so their finest features can be seen more clearly.

“It’s a very different way to do microscopy,” says Boyden, who is also a Howard Hughes Medical Institute (HHMI) investigator, a professor of brain and cognitive sciences and biological engineering, and a member of the Yang Tan Collective at MIT. “In contrast to the last 300 years of bioimaging, where you use a lens to magnify an image of light from an object, we physically magnify objects themselves.” Once a tissue is expanded, Boyden says, researchers can see more even with widely available, conventional microscopy hardware.

Boyden’s team introduced this approach, which they named expansion microscopy (ExM), in 2015. Since then, they have been refining the method and adding to its capabilities, while researchers at MIT and beyond deploy it to learn about life on the smallest of scales.

“It’s spreading very rapidly throughout biology and medicine,” Boyden says. “It’s being applied to kidney disease, the fruit fly brain, plant seeds, the microbiome, Alzheimer’s disease, viruses, and more.”

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Publication

Research

Chen, F.*, Tillberg, P.W.*, Boyden, E.S. (2015) Expansion Microscopy, Science 347(6221):543-548. (*, equal contribution)

Zhang YS*, Chang JB*, Alvarez MM, Trujillo-de Santiago G, Aleman J, Batzaya B, Krishnadoss V, Ramanujam AA, Kazemzadeh-Narbat M, Chen F, Tillberg PW, Dokmeci MR, Boyden ES**, Khademhosseini A.** (2016) Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications, Scientific Reports 6:22691. (* co-first authors, ** co-corresponding authors)

Schmidt, D., Tillberg, P. W.*, Chen, F.*, Boyden, E. S. (2014) A fully genetically-encoded protein architecture for optical control of peptide ligand concentration, Nature Communications, 5:3019. (* equal contribution)

Tillberg, P.W.*, Chen, F.*, Piatkevich, K.D., Zhao, Y., Yu, C.-C., English, B.P., Gao, L., Martorell, A., Suk, H.-J., Yoshida, F., DeGennaro, E.M., Roossien, D.H., Gong, G., Seneviratne, U., Tannenbaum, S.R., Desimone, R., Cai, D., Boyden, E.S. (2016) Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies, Nature Biotechnology 34:987–