Glycans are carbohydrate molecules bonded to proteins or other biomolecules. Researchers have adapted a low-temperature microscopy technology to study their structure. The potential for studying glycans can advance knowledge about diseases and how to optimally treat the people who have them.
Biological systems comprise many molecules in thousands of varieties.
For example, two proteins can be very similar and yet have different functions because they have different glycans bonded to them that modify their effects.
Glycans therefore strongly affect biological processes such as signalling pathways and cellular communication. However, researchers have not been able to study the structure of individual glycans and thereby discover how different glycan molecules give proteins different functions.
This is being remedied now after a team of researchers adapted a low-temperature microscopy technology to study the structure of individual glycans attached to many biomolecules. Researchers can now study the glycan-decorated molecules and also learn more about how they affect people’s health and disease.
“Thoroughly understanding the function of biomolecules requires mapping the variation among single molecules to help to determine their properties and function. Using an interdisciplinary approach, we can now analyse glycans bonded to proteins and other biomolecules at very high resolution at the single-molecule level,” explains a researcher involved in developing the technology, Kelvin Anggara, Senior Scientist, Max Planck Institute for Solid State Research, Stuttgart, Germany.
The research has been published in Science.
Glycans are biologically very important
Studying glycans bonded to proteins is useful because glycans are an essential organic building block present in all forms of life.
Think, for example, of two cells bumping into each other.
The cells have no eyes or ears, so the only way to determine how to act is through the interaction of molecules on the surface of the cells.
These molecules involve proteins to which different glycans bond, thereby enabling the cells to recognise each other.
This is why the immune system does not usually attack the body’s own cells, whereas it hammers away at pathogenic bacteria.
The problem for researchers has long been that studying the structure of glycans on proteins is very difficult.
For example, analysis of a biological sample will show that it contains many millions of glycans, and determining what the individual glycan molecules look like becomes almost impossible.
“This field has long struggled to understand the significance of the variation in the glycans, because the technology to study individual molecules and map their structure has not been available,” says Kelvin Anggara.
Microscope operates at minus 262°C
To solve this problem, the researchers adapted a method to study glycans at the single-molecule level.
The researchers further developed low-temperature scanning tunnelling microscopy, in which they place a glycan-decorated biomolecule on a surface and then visualise the biomolecule using a powerful microscope operating in a vacuum and at minus 262°C.
This microscopy technology eliminates all interference, enabling the precise structure of the individual glycans to be studied and how they are attached to proteins, lipids and other biomolecules.
The technology for studying glycans is not new, although the researchers have modified it slightly to make it work with biomolecules. The new invention comprises developing the technology to get the biomolecules to settle on the solid surface without damaging their structure.
“Scanning tunnelling microscopy was invented in the 1980s and has been used for many years to characterise the microscopic structure of metal surfaces in nanometres. It is very effective for studying things at the nanoscale or at the near-atomic level. But although the technology is well known from physics, it has not been used in biology before. We bridged the two research fields to solve an existing problem in biological research,” explains Kelvin Anggara.
May improve understanding of various diseases and treatment
Kelvin Anggara says that the technology opens up entirely new fields of research that may be important for understanding diseases and developing drugs.
For example, researchers will now be able to map the structure of cancer-specific glycan molecules on the surface of cancer cells and then design drugs that bind specifically to the glycan structure present only on the surface of cancer cells.
The technology can also be used to develop diagnostic tools to identify cancer cells or other types of pathogenic proteins and lipids, which may be important for understanding diseases and treating the people who have them.
“Some glycans may make the task easier or more difficult for the cellular machines that recognise or bind to cells. The potential of using this technology to study biostructures is that we can learn more about biology at the molecular level and can use this understanding to learn about diseases and how to treat the people who have them,” concludes Kelvin Anggara.