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Structure meets function: Glycocalyx analyzed at molecular level for first time

The glycocalyx surrounds each cell in the human body like a coat. This complex sugar layer plays a key role in the progression of numerous diseases, such as cancer and autoimmune diseases.

Researchers at the Max Planck Institute for the Science of Light (MPL) have succeeded for the first time in imaging individual sugars within the glycocalyx at molecular resolution and linking their spatial arrangement to their biological function. The findings, recently in the journal Nature Nanotechnology, open up completely new perspectives for understanding this important cell structure—with far-reaching consequences for diagnosis and therapy.

The glycocalyx is the cell's "doorkeeper": everything that approaches the cell interacts with it first. In recent years, glycocalyx has increasingly become the focus of biomedical research, because it influences numerous processes related to health and disease. Nevertheless, it has not been possible to link its spatial organization to its biological function, because it takes place on a scale of only one nanometer, a size that could not be made visible using previous methods.

Now, scientists at MPL have achieved a breakthrough using a special microscopy method in combination with a particular chemical labeling technique—individual sugar molecules could be visualized in the glycocalyx on the cell surface.

To achieve this, the researchers combined a special localization microscopy method (Resolution Enhancement by Sequential Imaging, RESI) with bioorthogonal chemistry in which the cell's metabolism is used to attach specific markers to target structures. The research was conducted cooperatively between Leonhard Möckl's research group and the Jungmann research group at the Max Planck Institute of Biochemistry in Martinsried.

The high-precision resolution in the range of a single nanometer allows scientists not only to count sugars and understand their interactions, but also to record their arrangement and communication in the natural environment of the cell. Like a map, this reveals the density of individual sugars at different locations in the cell and how this arrangement changes in the course of cellular events.

"This result is a long-standing goal for me," says Prof. Leonhard Möckl, head of the MPL research group Â鶹ÒùÔºical Glycosciences. "I considered how to understand the relationship between glycocalyx and cells as early as during my doctoral studies. Even back then, I was convinced that it could only work if we understood how the glycocalyx is organized at the molecular level. The fact that we can now depict the organization of individual sugars is a dream come true."

The results now enable functional conclusions to be drawn about cellular processes—such as how genetic mutations during cancer development alter the glycocalyx—and open up new avenues for clinical applications in diagnostics and therapy.