IMAGING ONE SUGAR AT THE TIME“Our concept was to use the same sugars that interact with cells as microscopy probes”, explains Lorenzo Albertazzi, associate professor and leader of the Nanoscopy for Nanomedicine group. “We didn’t need to change the building blocks”. The interaction of sugars with cells is weak, making it challenging to study with conventional fluorescence techniques. “We actually need weak interactions for our microscopy method”, emphasizes Riera. “It’s a perfect match. The imaging is based on reversible interactions: fluorescently-labelled sugar probes bind for a very short time to the cell’s lectins and unbind. This process is repeated over time, enabling the detection of individual sugar-lectin interactions.” Interesting properties surfaced from this study. “We could see that different sugar structures present different binding kinetics, bringing us closer to understanding their structure-activity relationship.”
Our methods could be used to understand better how immune cells recognize certain sugars over others.
THE SUGAR SOS CODEIn some cases, sugars can signal danger and provoke an immune activation. This signaling happens when the body recognizes the sugars from a pathogen’s membrane. “Immune cells recognize the difference between our native sugars and the ones from a pathogen by recognizing the sugar patterns. ” Clarifies Riera. “These patterns depend on the sugar arrangement”. Are sugars a candidate to develop more potent vaccines? “We can use sugars to trick the immune system into thinking it’s a danger signal and stimulate an immune response, similar as in vaccines”, he explains. However, there is a sweet spot to get it exactly right. “If you use the wrong sugars, the immune response will be very different”, specifies Albertazzi. But more research is needed. “Our methods could be used to understand better how immune cells recognize certain sugars over others”, concludes Albertazzi.
Reference article: Riera, R., Hogervorst, T.P., Doelman, W. et al. Single-molecule imaging of glycan–lectin interactions on cells with Glyco-PAINT. Nat Chem Biol 17, 1281–1288 (2021).