Targeting of Liposomes Carrying Recombinant Fragments of Platelet Membrane Glycoprotein Ibα to Immobilized von Willebrand Factor under Flow Conditions

Abstract

Liposomes with covalently bound recombinant fragments of platelet membrane glycoprotein Ibα that retain the von Willebrand factor (vWf)-binding function (rGPIbα–liposomes) were prepared. Their interactions with an immobilized vWf surface under flow conditions were evaluated with a recirculating flow chamber, mounted on an epifluorescence microscope, which allows real-time visualization of fluorescence-labeled liposomes interacting with the surface. The interaction of rGPIbα–liposomes with the vWf surface was directly related to shear rate. At high densities of rGPIbα and vWf, rGPIbα–liposomes establishing contact with the vWf surface exhibited continuous displacement with decreased velocity relative to the hydrodynamic flow, depending on receptor density and matrix concentration. At lower densities of rGPIbα and vWf, rGPIbα–liposomes stopped only transiently, in the millisecond range, on the surface. This is the first study to demonstrate that the targeting of rGPIbα–liposomes is specific to the vWf surface under flow conditions.