The energetics, stoichiometry, and structure of poly(amidoamine) (PAMAM) dendrimer-phospholipid interactions were measured with isothermal titration calorimetry (ITC), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and molecular dynamics (MD) simulations. Dendrimers of sixth-generation and smaller interacted with the lipids at an average stoichiometry and enthalpy proportional to the number of primary amines per dendrimers (4.5 ± 0.1 lipids/primary amine and 6.3 ± 0.3 kJ/mol of primary amines, respectively). Larger dendrimers, however, demonstrated a decreased number of bound lipids and heat release per primary amine, presumably due to the steric restriction of dendrimer deformation on the lipid bilayer. For example, eighth-generation PAMAM dendrimers bound to 44% fewer lipids per primary amine and released 63% less heat per primary amine as compared to the smaller dendrimers. These differences in binding stoichiometry support generation-dependent models for dendrimer-lipid complexation, which are consistent with previously observed generation-dependent differences in dendrimer-induced membrane disruption. Dendrimers of seventh-generation and larger bound to lipids with an average stoichiometry consistent with each dendrimer having been wrapped by a bilayer of lipids, where as smaller dendrimers did not.

In this manuscript we report the crosslinking of pre-existing macromolecules in solution through the use of photoactive benzophenone chromophores. We show that a bifunctional crosslinker composed of two benzophenone chromophores as well as a single benzophenone chromophore crosslink poly (butadiene) and poly (ethylene oxide) in solution to form insoluble gels when irradiated with UV light. The molecular weight between crosslinks of the photogenerated gels was compared for the two crosslinkers, for an equivalent amount of benzophenone chromophores in each solution, by measuring the swelling ratio of the gels formed.Gels formed from the bifunctional benzophenone crosslinker were shown to contain more than twice as many crosslinks compared to gels formed from the crosslinker composed of a single benzophenone chromophore. EPR measurements of a nitroxide derivative absorbed into the gels further supported a higher crosslink density for the gels formed from the bifunctional benzophenone crosslinker.

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The folic acid-folate receptor recognition interaction has been exploited for targeted drug delivery, yet the detailed mechanism of this binding is unknown. Here, atomic force microscopy was employed to measure the folic acid-folate binding protein interaction. After conjugating a flexible poly(ethylene glycol) linker to folic acid and attaching this to an AFM tip, a controlled mechanical force was applied to disrupt the binding interaction. The amount of force required to cause rupture at various force loading rates were measured. The rupture force dependency on the loading rate characterizes the energy landscape of the single molecule interaction between folic acid and folate binding protein.Control experiments were performed to ascertain the specificity of the FA-FBP single molecule interaction. The use of dynamic force spectroscopy to investigate the details of this binding interaction provides new insight to guide the design of folate receptor-targeting molecules.

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