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We show that assemblies comprising anchored polymers with a gradual variation of grafting densities on solid substrates can be generated by first covering the substrate with a molecular gradient of the polymerization initiator, followed by polymerization from the substrate-bound initiator centers (“grafting from”). We apply this technique to prepare grafting density gradients of poly(acrylamide) (PAAm) on flat silica substrates. We demonstrate that using the grafting density gradient geometry, the mushroom-to-brush transition can be accessed on a single sample. This transition is detected by monitoring the dependence of the thickness of the grafted PAAm in a good solvent using variable angle spectroscopic ellipsometry. Wettability experiments performed on the gradient PAAm substrate provide complementary information about the nature of the mushroom-to-brush transition.

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Type 5 adenovirus (Ad5) is a human pathogen that has been widely developed for therapeutic uses, with only limited success to date. We report here the novel finding that human erythrocytes present Coxsackie virus-adenovirus receptor (CAR) providing an Ad5 sequestration mechanism that protects against systemic infection. Interestingly, erythrocytes from neither mice nor rhesus macaques present CAR. Excess Ad5 fiber protein or anti-CAR antibody inhibits the binding of Ad5 to human erythrocytes and cryo-electron microscopy shows attachment via the fiber protein of Ad5, leading to close juxtaposition with the erythrocyte membrane. Human, but not murine, erythrocytes also present complement receptor (CR1), which binds Ad5 in the presence of antibodies and complement. Transplantation of human erythrocytes into nonobese diabetic/severe combined immunodeficiency mice extends blood circulation of intravenous Ad5 but decreases its extravasation into human xenograft tumors. Ad5 also shows extended circulation in transgenic mice presenting CAR on their erythrocytes, although it clears rapidly in transgenic mice presenting erythrocyte CR1. Hepatic infection is inhibited in both transgenic models. Erythrocytes may therefore restrict Ad5 infection (natural and therapeutic) in humans, independent of antibody status, presenting a formidable challenge to Ad5 therapeutics. “Stealthing” of Ad5 using hydrophilic polymers may enable circumvention of these natural virus traps.

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