Researchers have developed a microscopy-based method that maps the organization of glycans – sugar molecules found on the cell surface – at nanometer-scale resolution and links those patterns to cellular behavior and disease state. The approach, called “glycan atlassing,” was reported in Nature Nanotechnology.
The glycocalyx, the sugar-rich coating that surrounds cells, plays an important role in immune signaling, cell adhesion, inflammation, and cancer biology. Changes in glycosylation are well recognized in tumors and immune activation, but studying how these molecules are spatially organized on cells has been technically difficult. Conventional microscopy lacks sufficient resolution, while methods such as mass spectrometry do not preserve spatial relationships within tissues.
In this study, investigators combined DNA-tagged lectins, metabolic glycan labeling, and super-resolution microscopy to create detailed maps of glycan distribution on cells and tissues. They then used computational analysis to identify recurring glycan patterns associated with specific cellular states.
The researchers tested the method in cultured epithelial cells, primary neurons, human immune cells, and human breast cancer tissue. Across these systems, the technique was able to distinguish different biologic conditions based on glycan organization alone.
In breast epithelial cell models, glycan patterns differed between normal and transformed cells and also changed during epithelial-to-mesenchymal transition, a process associated with cancer progression.
In immune cells, the method detected rapid changes in the glycocalyx after activation. Natural killer cells exposed to lung cancer cells showed measurable glycan reorganization within minutes, suggesting that immune cell surface architecture changes dynamically during immune responses. Activated CD4-positive T cells and neutrophils also displayed distinct glycan signatures compared with resting cells.
The technique was also applied to human breast adenocarcinoma tissue sections. Tumor and non-tumor regions demonstrated different glycan organization patterns, and tumor tissue showed greater heterogeneity.
Although the approach is currently research-focused and technically complex, the findings highlight the potential diagnostic relevance of glycocalyx architecture. The authors suggest that nanoscale glycan patterns may eventually help classify tumors, characterize immune activation states, or provide additional biologic information beyond conventional histology and molecular testing.
The investigators also noted current limitations, including the need for specialized imaging equipment, labor-intensive analysis, and a limited number of glycan targets.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
