Many neurological conditions, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders where cell death results in the observed clinical symptoms. There is no cure for either MS or ALS and limited treatment options for both. Recently we discovered that certain IgM isotype antibodies have profound effects in vitro and therapeutic effects in animal models of MS and ALS. These antibodies bind to glycolipids found in the membranes of neurons or oligodendrocytes. The mouse IgMs O1 and O4 promote remyelination and bind to galactocerebroside (GalC) and sulfatide, respectively. GalC and sulfatide are found in oligodendrocyte membranes at various stages of development. A human recominbinant IgM, rHIgM12, binds a ganglioside (GT1b) found on neurons and promotes neurite outgrowth, improves locomotor activity in ALS and MS mouse models and prolongs lifespan in ALS model mice. We used nanohole surface plasmon resonance (SPR) to characterize the binding kinetics and affinity between IgMs and glycolipids in supported lipid bilayers (SLBs). The nanohole array SPR sensor chips were fabricated in silver films by nanoimprint lithography and template stripping followed by atomic layer deposition of a silica shell to facilitate SLB formation. PDMS microfluidics were used to deliver lipid vesicles and antibodies to the sensor. We determined that O1, O4 and rHIgM12 bind their glycolipid receptors with unusually small dissociation constants (< 10 nM) for natural IgMs. Also, by coating gold nanoparticles with lipid membranes we were able to detect antibody-glycolipid binding using localized surface plasmon resonance (LSPR) spectroscopy with the goal of observing single antibody-nanoparticle binding events.

Interactions between neurotherapeutic IgM antibodies and glycolipids characterized by plasmonic nanohole arrays and localized surface plasmon resonance

248th National Meeting (2014)

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