Unraveling the cell’s sweet spot from nature

In a recent Nature chemical biology paper, a team of researchers from ICMS/TUE and IBEC, together with researchers from Leiden University unravel the interactions of individual sugar molecules with cells using super-resolution microscopy. The paper appeared on the cover of the November issue of the journal.

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Sugars interact with the cell surface through sugar-binding proteins called lectins. These interactions play a fundamental role in many of the cell’s biological processes. One important function is the modulation of the immune response towards an outside threat.  

PhD candidate Roger Riera, from the Nanoscopy for Nanomedicine group at IBEC and TUE led by Lorenzo Albertazzi, investigates cell surface receptors and their interaction with molecules using novel microscopy techniques. The idea to image sugar-lectin interactions started from a long ongoing collaboration with Leiden University researchers. “We bring together two fields: our collaborators develop sugar probes and we have the microscopy expertise”, says Riera.  

 

 

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.

Lorenzo Albertazzi 

THE SUGAR SOS CODE 

In 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 Biol17, 1281–1288 (2021).