Targeting of liposomes carrying recombinant fragments of platelet membrane glycoprotein Ibα 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 function (rGPIb alpha-liposomes) were prepared. Their interactions with an immobilized vWf surface under how conditions were evaluated with a recirculating how chamber, mounted on an epifluorescence microscope, which allows real-time visualization of fluorescence-labeled liposomes interacting with the surface. The interaction of rGPIb alpha-liposomes with the vWf surface was 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 hydrodynamic how, depending on receptor density and matrix concentration. At lower densities of rGPIb alpha and vWf, rGPIb alpha-liposomes stopped only transiently, in the millisecond range, on the surface. This is the first study to demonstrate that the targeting of rGPIb alpha-liposomes is specific to the vWf surface under how conditions. (C) 2000 Academic Press.