Synthetic, virus-like capsids are of interest for applications ranging from environmental sensing to therapeutic delivery De novo design of large, virus-like constructs, however, poses a formidable challenge to molecular self-assembly. A new method developed by Whitesides and coworkers known as mesoscale self-assembly affords access to more sizeable aggregates in the micron to millimeter range. Using the meso-scale strategy I will prepare mesoscopic capsid structures capable of reversibly encapsulating hydrophilic material. Incorporation of ionizable groups into subunit assembly surfaces, using self-assembling monolayers should allow control of capsid assembly through electrostatic repulsion, mimicking pH- triggered disassembly of the influenza virion. Within a therapeutic context, pH-controlled subunit dissociation could be used to selectively delivery capsid contents to phagocytotic cells such as macrophages. Finally, using appropriately designed subunits I will study the cooperativity of mesoscopic capsid assembly. Given the role of cooperativity in regulating biomolecular interactions, I expect that demonstration of this concept in mesoscopic systems which mimic certain biological activities will prove of considerable scientific value.
