Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.

Multivalency is the increase in avidity resulting from the simultaneous interaction of multiple ligands with multiple receptors. This phenomenon, seen in antibody-antigen and virus-cell membrane interactions, is useful in designing bioinspired materials for targeted delivery of drugs or imaging agents. While increased avidity offered by multivalent targeting is attractive, it can also promote nonspecific receptor interaction in nontarget tissues, reducing the effectiveness of multivalent targeting. Here, we present a thermal targeting strategy--dynamic affinity modulation (DAM)--using elastin-like polypeptide diblock copolymers (ELP(BC)s) that self-assemble from a low-affinity to high-avidity state by a tunable thermal "switch", thereby restricting activity to the desired site of action. We used an in vitro cell binding assay to investigate the effect of the thermally triggered self-assembly of these ELP(BC)s on their receptor-mediated binding and cellular uptake. The data presented herein show that (1) ligand presentation does not disrupt ELP(BC) self-assembly; (2) both multivalent ligand presentation and upregulated receptor expression are needed for receptor-mediated interaction; (3) increased size of the hydrophobic segment of the block copolymer promotes multivalent interaction with membrane receptors, potentially due to changes in the nanoscale architecture of the micelle; and (4) nanoscale presentation of the ligand is important, as presentation of the ligand by micrometer-sized aggregates of an ELP showed a low level of binding/uptake by receptor-positive cells compared to its presentation on the corona of a micelle. These data validate the concept of thermally triggered DAM and provide rational design parameters for future applications of this technology for targeted drug delivery.

Constructal Design of Energy Systems

This dissertation shows the use of Constructal law to find the relation between the morphing of the system configuration and the improvements in the global performance of the complex flow system. It shows that the better features of both flow and heat transfer architecture can be found and predicted by using the constructal law in energy systems. Chapter 2 shows the effect of flow configuration on the heat transfer performance of a spiral shaped pipe embedded in a cylindrical conducting volume. Several configurations were considered. The optimal spacings between the spiral turns and spire planes exist, such that the volumetric heat transfer rate is maximal. The optimized features of the heat transfer architecture are robust. Chapter 3 shows the heat transfer performance of a helically shaped pipe embedded in a cylindrical conducting volume. It shows that the optimized features of the heat transfer architecture are robust with respect to changes in several physical parameters. Chapter 4 reports analytically the formulas for effective permeability in several configurations of fissured systems, using the closed-form description of tree networks designed to provide flow access. The permeability formulas do not vary much from one tree design to the next, suggesting that similar formulas may apply to naturally fissured porous media with unknown precise details, which occur in natural reservoirs. Chapter 5 illustrates a counterflow heat exchanger consists of two plenums with a core. The results show that the overall flow and thermal resistance are lowest when the core is absent. Overall, the constructal design governs the evolution of flow configuration in nature and energy systems.