The interactions between axons and myelin in the nervous system are mediated by a number of protein-protein and lipid-protein interactions. One such interaction is that between the GD1a and GT1b gangliosides on axons and myelin-associated glycoprotein (MAG) on myelin. MAG is a transmembrane protein that is a potent inhibitor of neuron growth. While the ganglioside-MAG interactions have been described, quantitative evaluation of ganglioside-MAG binding is lacking. Here we use a quartz crystal microbalance (QCM-D) biosensor to characterize these interactions, and we examine how antibodies associated with Guillain-Barre syndrome disrupt these interactions. The QCM sensor chip is functionalized with a supported lipid bilayer (SLB) containing Ni-NTA lipids that are able to capture histidine-tagged MAG. Then small (approx. 100 nm) vesicles bearing various concentrations of GD1a or GT1b are injected. Binding of the vesicles to the MAG-functionalized SLB results in a negative shift in the QCM frequency signal. The vesicle binding rate increases as the ganglioside concentration on vesicles increases. As the ganglioside concentration is increased, the rate of vesicle dissociation from the surface decreases due to multivalency effects. We also show that antibodies similar to those found in Guillain-Barre syndrome patients can inhibit interactions between MAG and gangliosides in a concentration-dependent manner. These results shed light upon how multiple weak ganglioside-MAG interactions can firmly adhere membranes together, and how pathogenic antibodies might cause dysfunction at the axon-myelin interface.

Characterizing interactions between supported lipid bilayer membranes and vesicles mediated by myelin-associated glycoprotein binding to gangliosides

ACS Fall 2020 Virtual Meeting

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