Biomimetic Formation and Tuning of a Cell Surface Heparan Sulfate Network: Approach on Deciphering the...

Area of Science:

• Biochemistry
• Biophysics
• Cell Biology

Background:

• The cell surface glycocalyx, a network of glycoproteins and proteoglycans, is crucial for biological functions.
• Glycosaminoglycans (GAGs) form the 3D architecture of the glycocalyx, mediating diverse biological processes.
• Understanding GAG structure and protein interactions is vital for deciphering molecular mechanisms, but conventional sensors fail to capture its complexity.

Purpose of the Study:

• To develop a biomimetic platform simulating the glycocalyx microenvironment for studying GAG-protein interactions.
• To investigate the impact of heparin density, spatial distribution, and chain length on SARS-CoV-2 spike protein binding.
• To elucidate the binding mechanisms between heparin and viral spike proteins.

Main Methods:

• Construction of a 3D ordered interference substrate with surface-modified heparin.
• Utilizing an ordered porous layer interferometry (OPLI) platform.
• Employing experimental and computer simulation methods, including molecular docking and thermodynamic experiments.

Main Results:

• A medium heparin density was found to maximize the binding strength of the SARS-CoV-2 spike protein.
• Increased 3D spatial distribution density of heparin enhanced its affinity for the spike protein.
• Hydrogen bonds, not electrostatic interactions, were identified as the primary drivers of binding strength.

Conclusions:

• The developed OPLI platform successfully recreates the glycocalyx microenvironment, offering a biomimetic approach for GAG-protein interaction studies.
• This research deepens the molecular understanding of viral infections, specifically SARS-CoV-2 binding to the host cell surface.
• The study provides a foundational methodology for GAG code analysis and the development of novel therapeutics.