Detection and Characterization of Vesicular Gangliosides Binding to Myelin-Associated Glycoprotein on Supported Lipid Bilayers

Abstract

In the nervous system, a myelin sheath that originates from oligodendrocytes or Schwann cells wraps around axons to facilitate electrical signal transduction. The interface between an axon and myelin is maintained by a number of biomolecular interactions. Among the interactions are those between GD1a and GT1b gangliosides on the axon and myelin-associated glycoprotein (MAG) on myelin. Interestingly, these interactions can also inhibit neuronal outgrowth. Ganglioside–MAG interactions are often studied in cellular or animal models where their relative concentrations are not easily controlled or in assays where the gangliosides and MAG are not presented as part of fluid lipid bilayers. Here, we present an approach to characterize MAG–ganglioside interactions in real time, where MAG, GD1a, and GT1b contents are controlled and they are in their in vivo orientation within fluid lipid bilayers. Using a quartz crystal microbalance with dissipation monitoring (QCM-D) biosensor functionalized with a supported lipid bilayer (SLB) and MAG, we detect vesicular GD1a and GT1b binding and determine the interaction kinetics as a function of vesicular ganglioside content. MAG-bound vesicles are deformed similarly, regardless of the ganglioside or its mole fraction. We further demonstrate how MAG–ganglioside interactions can be disrupted by antiganglioside antibodies that override MAG-based neuron growth inhibition.

Unraveling How Multivalency Triggers Shape Deformation of Sub-100 nm Lipid Vesicles

“…Multivalent binding interactions are widely found in biological systems, − and well-known examples involving biological nanoparticles include virion and exosome attachment to cellular membrane interfaces. − These interactions can have significant biomedical implications, such as affecting the degree of virus transmissibility (see, e.g., refs and ), and have also inspired the biomimetic design of therapeutic and diagnostic nanoparticles and tools based on receptor mimicking. − While multivalent ligand–receptor interactions have been extensively studied in the context of biological nanoparticle attachment, − an emerging and less well understood topic concerns the resulting shape changes of attached nanoparticles , (see also discussion in refs and ). When soft-matter biological and biomimetic nanoparticles such as membrane-enveloped virions, exosomes, and lipid vesicles attach to a receptor-functionalized surface, they can, in principle, undergo deformation that is dictated by the balance of the multivalent binding interaction and membrane bending energies − (see also examples of shape changes in the receptor-functionalized surface itself − ).…”

Targeting of Pseudomonas aeruginosa cell surface via GP12, an Escherichia coli specific bacteriophage protein

“…QCM-D is a surface-based sensing technique that relies on a piezoelectric quartz crystal that is coupled to an electric circuit 11 . A major advantage of QCM-D is that it enables label-free and real-time monitoring of biomolecules or particle adsorption, and it can be used to characterize interactions between an adsorbed receptor layer and particles, such as liposomes or viruses 12 – 14 . Adsorption of the receptor layer to the sensor and binding of liposomes to the receptor layer both result in mass accumulation on the sensor surface, which manifests as negative shifts in the resonant frequency of the quartz crystal.…”

Effects and molecular mechanisms of Achyranthes bidentata polypeptide k on proliferation of Schwann cells

“…After peripheral nerve injury, proliferated SCs migrate along the basement membrane to the damaged segment to form the Büngner area, and secrete nutritional factors to guide the axon to grow distally (17)(18)(19). SCs can also promote the process of myelination after peripheral nerve injury (20,21), which is very important for the timely and accurate transmission of information between the brain and body parts (22). Therefore, promoting the proliferation of SCs contributes to the repair and functional recovery of peripheral nerves.…”