Targeting of liposomes carrying recombinant fragments of platelet membraneglycoprotein Ib alpha to immobilized von Willebrand factor under flow conditions

Liposomes with covalently bound recombinant fragments of platelet membrane glycoprotein Ib alpha that retain the von Willebrand factor (vWf)-binding f unction (rGPIb alpha-liposomes) were prepared. Their interactions with an i mmobilized vWf surface under how conditions were evaluated with a recircula ting how chamber, mounted on an epifluorescence microscope, which allows re al-time visualization of fluorescence-labeled liposomes interacting with th e surface. The interaction of rGPIb alpha-liposomes with the vWf surface wa s directly related to shear rate. At high densities of rGPIb alpha and vWf, rGPIb alpha-liposomes establishing contact with the vWf surface exhibited continuous displacement with decreased velocity relative to the hydrodynami c how, depending on receptor density and matrix concentration. At lower den sities of rGPIb alpha and vWf, rGPIb alpha-liposomes stopped only transient ly, in the millisecond range, on the surface. This is the first study to de monstrate that the targeting of rGPIb alpha-liposomes is specific to the vW f surface under how conditions. (C) 2000 Academic Press.