Balloon-like Particles help reveal Hidden Sugar Signals in the Immune System

Understanding how immune cells recognize one another is essential for developing better treatments for cancer, autoimmune disease, and inflammation. Many of the signals they use involve glycans, the complex sugars that coat cell surfaces. However, these sugar-based interactions are often difficult to study.

• Reported in Science Advances, GlycoNet researchers at the University of Alberta have developed a tool that makes these interactions easier to detect. The work was led by PhD candidate Zeinab Jame-Chenarboo in the lab of GlycoNet investigator and professor Matthew Macauley, and also involved collaboration with the lab of GlycoNet investigator and professor Ratmir Derda. Together, the research team created “Siglec-liposomes.” These tiny, balloon-like particles help detect nuanced molecular interactions, shedding light on how immune cells communicate through their sugar coatings.

“The liposomes are like tiny soap bubbles made of fat. The inside is empty, and on the outside we decorate them with Siglecs,” explains Jame-Chenarboo, who is first author on the paper.

Siglecs are immune receptors that recognize specific glycans (complex sugar chains) on surrounding cells. However, each individual interaction between a Siglec and a glycan is weak, resulting in a faint signal that can be easily missed or misinterpreted with standard tools. In the body, this limitation is overcome when Siglecs cluster densely on the cell surface, strengthening the overall interaction and creating a multivalent effect.

To replicate this natural effect with the liposome probes, the GlycoNet team attached roughly 160 Siglec molecules to each liposome, forming a multivalent display that behaves similarly to a real immune cell surface. They also expressed the receptors in cells engineered not to have their usual sialic acid sugars. Without those sugars, the Siglecs do not bind to themselves, leaving them fully available to detect the glycans that researchers want to study.

Distinct sugar “fingerprints” across immune cells

With these probes, the team mapped glycan patterns on several major human immune cell types—including T cells, B cells, natural killer cells, monocytes and neutrophils. Each Siglec-liposome displayed a unique binding pattern, revealing subtle variations between immune cells that are often missed by more conventional methods. These distinctions could help explain why immune cells behave differently across various diseases and may guide strategies for more targeted treatments.

Nudging T cells toward greater activity

Beyond detection, the team explored whether Siglec-liposomes could influence immune behaviour. In laboratory experiments, human T cells exposed to Siglec-7 liposomes multiplied more quickly than usual. This increase depended on an enzyme required to build the glycan structures that Siglec-7 recognizes; without that enzyme, the effect disappeared. The researchers also saw that Siglec-7 was far more potent when grouped on a liposome surface than when present as a free protein, highlighting the importance of multivalency.

“Siglecs are important immune regulators, so seeing Siglec-7 increase T-cell activity was really interesting to us,” Jame-Chenarboo says. “We don’t know the full mechanism yet, but it suggests these receptors may guide immune responses in ways we haven’t fully explored.”

An unexpected finding in the brain and future potential

The researchers tested the probes in living mice to see how they behave in a complex biological environment. When Siglec-7 liposomes were injected into the bloodstream, they unexpectedly accumulated on blood vessels in the brain. Follow-up experiments showed that this binding depended on mucin-type molecules, which are large, heavily sugar-coated proteins found on many tissues. The finding is early, but it suggests that Siglec-7, or tools based on it, might one day help direct therapies toward the brain, a notoriously difficult region to target.

Siglec-liposomes can be customized in many ways, providing a valuable tool for future research, and because they remain stable in living systems, they offer a way to study glycan interactions under realistic biological conditions.

Read the scientific publication in Science Advances.

The research was funded by GlycoNet, the Canadian Institutes of Health Research (CIHR), and the Natural Sciences and Engineering Research Council (NSERC).

Original source here.