Polyvalent interactions of HIV-gp120 protein and nanostructures of carbohydrate ligands

This paper presents the initial effort in anti-HIV infection using glycosphingolipid-based nanostructures. HIV infection of CD4 negative cells is initiated by the binding of the viral envelope glycoprotein gp120 to galactosylceramide (GalCer), a glycosphingolipid that serves as the cellular receptor for viral recognition. A series of nanostructures of GalCer are designed and produced using an AFM-based lithography method known as nanografting. The geometry dependence of recombinant gp120 binding to these nanostructures is monitored using high-resolution AFM imaging. Gp120 molecules are found to favor binding sites that allow for polyvalent interactions. Increased adsorption at the intersection of two lines, or between two parallel lines with matching separation for trimeric binding, strongly suggests that trivalent interactions are dominant in gp120-GalCer nanostructure interactions. Systematic distance-dependence studies, using parallel nanolines with various separations, reveal a separation of 4.8 nm, matching the separation of V3 loops in gp120 trimers. This investigation demonstrates that nanotechnology provides a powerful tool for investigating and guiding polyvalent interactions among biological systems.