Selective Glycan Presentation in Liquid-Ordered or -Disordered Membrane Phases and its Effect on Lectin Binding.

Area of Science:

• Biochemistry
• Cell Biology
• Biophysics

Background:

• Glycan-protein interactions are crucial for biological processes, occurring at the cell surface glycocalyx.
• The glycocalyx's complexity, dynamism, and heterogeneity pose challenges for studying its function.
• Understanding these interactions is key to fields ranging from infection to developmental biology.

Purpose of the Study:

• To develop a model system for controlling the spatial organization and heterogeneity of glycans at the cell surface.
• To investigate how the phase localization of glycans influences protein receptor recruitment and binding.
• To provide experimental evidence for the role of lipid rafts in enhancing glycan-receptor interactions.

Main Methods:

• Development of glycan mimetics with lipid moieties for phase partitioning in giant unilamellar vesicles (GUVs).
• Utilizing GUVs as simplified cell membrane models to mimic lipid rafts (liquid-ordered, Lo) and disordered phases (Ld).
• Assessing protein receptor (lectin) binding to distinct glycan presentations within the GUV membrane models.

Main Results:

• The developed model allows controlled spatial organization and heterogeneity of glycan moieties.
• Phase localization of glycan mimetics significantly influences protein receptor recruitment to the membrane.
• Glycan-conjugates in the ordered phase (lipid rafts) showed enhanced lectin binding compared to the disordered phase.

Conclusions:

• The study presents a novel platform for systematically investigating glycan presentation in biological systems.
• Experimental evidence demonstrates that glycan accumulation in lipid rafts enhances receptor binding affinity.
• These findings offer deeper insights into the functional mechanisms of the glycocalyx and cell surface recognition.