New Tissue Expansion Technique Boosts Molecular Imaging to Single-Cell Resolution.

A pioneering new technique that expands tissue samples is offering scientists an unprecedented view into the molecular landscape of cells. By combining tissue expansion with mass spectrometry imaging, a multi-institutional research team has successfully mapped the distribution of hundreds of biomolecules—such as lipids, proteins, and metabolites—at single-cell resolution while preserving their native environment. The study, recently published in Nature Methods, opens up promising avenues for studying biological processes in health and disease.

Biologists have long struggled to visualize the full range of biomolecules within intact tissue samples. While imaging techniques like microscopy can reveal molecules in cells, they are typically limited to a few targets at a time and often cannot detect certain molecules, including lipids. Mass spectrometry, on the other hand, can identify a broad array of molecules but lacks spatial context when applied to unsectioned tissue.

Mass spectrometry imaging (MSI) addresses some of these issues by detecting numerous molecules in intact tissues. However, MSI traditionally lacks the spatial resolution needed to reach the level of individual cells. This limitation has been a key obstacle for researchers like Meng Wang, a Senior Group Leader at Janelia, who investigates how tissues change during aging.

To solve this problem, Wang collaborated with Paul Tillberg, a Principal Scientist at Janelia and co-developer of expansion microscopy—a technique he helped create at MIT that uses swellable hydrogels to enlarge biological samples uniformly. By integrating this expansion method with MSI, the team enhanced the imaging resolution without compromising the molecular integrity of the samples.

Unlike earlier expansion methods that could degrade biomolecules, the team’s modified approach maintains tissue integrity while gradually enlarging the samples. This allows scientists to conduct untargeted MSI with the spatial resolution approaching that of optical microscopy.

The researchers applied this innovative method to study the cerebellum, revealing that lipids, peptides, proteins, glycans, and other small molecules are not evenly distributed as once assumed. Instead, each cerebellar layer displayed a unique molecular profile. They also successfully tested the technique on other tissues, including the kidney, pancreas, and tumors, discovering significant variations in biomolecular distribution, particularly in tumor samples. These findings could lead to new insights into tumor biology and drug development.

Wang emphasized that the method’s accessibility is one of its strengths. It requires no specialized equipment beyond a standard MSI system and can be readily adopted by labs worldwide. The researchers also provided detailed protocols to support widespread implementation.

“This technology lets us examine molecular patterns in their native context,” Wang noted. “Understanding these patterns can reveal how biomolecules influence development, aging, and disease.”

With its high resolution and broad applicability, this technique stands to become a vital tool in biological research, offering new clarity into the molecular underpinnings of life.

Source:https://phys.org/news/2025-04-technique-tissues-hundreds-biomolecules-cells.html

This is non-financial/medical advice and made using AI so could be wrong.