Bottom-up Investigation of Spatiotemporal Glycocalyx Dynamics with Interferometric Scattering Microscopy

Area of Science:

• Cellular Biology
• Biophysics
• Glycobiology

Background:

• The glycocalyx, an extracellular organelle, plays a vital role in cellular processes, but its molecular mechanisms remain largely unknown.
• Understanding glycocalyx function requires advanced technologies for high-resolution investigation of its intricate environment.

Purpose of the Study:

• To establish an experimental platform for investigating glycocalyx dynamics at the nanometer and microsecond scales.
• To create tunable glycocalyx model systems for studying molecular-level principles.

Main Methods:

• Synthesized defined oligosaccharides and installed them on supported lipid bilayers to create model glycocalyx systems.
• Utilized interferometric scattering (iSCAT) microscopy to achieve high spatiotemporal resolution.
• Employed atomistic and coarse-grained molecular dynamics simulations for corroboration.

Main Results:

• Demonstrated a strong correlation between molecular glycan structure and the overall system dynamics.
• Provided the first direct experimental evidence linking glycan structure, organization, and dynamics.
• Developed tunable model systems with controllable properties for glycocalyx research.

Conclusions:

• The developed platform enables quantitative understanding of glycocalyx biology and physics at the molecular level.
• Findings offer a foundation for deciphering the fundamental principles governing glycocalyx function in health and disease.