No abstract

Nogo-A limits axon regeneration and functional recovery after central nervous system injury in adult mammals. Three regions of Nogo-A (Nogo-A-24, Nogo-66, and Nogo-C39) interact with the neuronal Nogo-66 receptor 1 (NgR1). Nogo-66 also interacts with a structurally unrelated cell surface receptor, paired immunoglobulin-like receptor (PirB). We show here that the other two NgR1-interacting domains, Nogo-A-24 and Nogo-C39, also bind to PirB with high affinity. A purified 22-kDa protein containing all three NgR1-and PirB-interacting domains (Nogo-22) is a substantially more potent growth cone-collapsing molecule than Nogo-66 for chick dorsal root ganglion neurons and mature cortical neurons. Moreover, Nogo-22 inhibits axon regeneration of mature cortical neurons in vitro more potently than does Nogo-66. Although all three NgR1-interacting domains of Nogo-A also interact with PirB, expression of PirB in mature cortical cultures is nearly undetectable. Consistent with a relatively minor role for PirB in mature cortical neurons, Nogo-22 inhibition of axon regeneration is abolished by genetic deletion of NgR1. Thus, NgR1 is the predominant receptor for Nogo-22 in regenerating cortical neurons.

Zwitterionomers containing less than 13 mol % zwitterion functionality were synthesized using free radical copolymerization of n-butyl acrylate (nBA) and sulfobetaine monomers. X-ray scattering results revealed a two-phase morphology, which is typical of random ionomers with an ionomer peak at q ∼1.5 nm -1 . Swelling studies in the ionic liquid (IL), 1-ethyl-3-methylimidazolium ethylsulfate (EMIm ES), showed an influence of zwitterionic structure on IL uptake. Zwitterionomer membranes were swollen to various IL contents, and the influence of IL on mechanical properties, morphology, and ionic conductivity was explored through dynamic mechanical analysis (DMA), X-ray scattering, and impedance spectroscopy, respectively. Results revealed that IL preferentially swelled the zwitterionic domains but was excluded from the matrix phase. Significant changes in mechanical properties and ionic conductivity were observed above a critical uptake of IL. Fundamental explorations of the interaction of ILs with sulfobetaine-containing copolymers may lead to the use of zwitterionomers in emerging membrane applications.

n-Butyl acrylate-based zwitterionomers and ionomers containing 3- [[2-(methacryloyloxy)ethyl](dimethyl)ammonio]-1-propanesulfonate (SBMA) and 2-[butyl(dimethyl)amino]ethyl methacrylate methanesulfonate (BDMAEMA MS), respectively, were synthesized using conventional free radical polymerization. Size-exclusion chromatography confirmed the molecular weights of the copolymers exceeded the critical molecular weight between entanglements (M e ) for poly(n-butyl acrylate). Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and atomic force microscopy (AFM) revealed that zwitterionomers promoted more welldefined microphase separation than cationic analogues. Dynamic mechanical analyses (DMA) of the copolymers showed a rubbery plateau region due to physical cross-links between charges for zwitterionomers only. Since SBMA and BDMAEMA MS have very similar chemical structures, we attributed improved microphase separation and superior elastomeric performance of the zwitterionomers to stronger association between covalently tethered charged pairs.