Self-Assembly of Multicomponent Nanostructures

Nature spontaneously organizes biomolecules, including proteins, cell membranes, and tissues into complex, highly ordered structures. Researchers will harness this process to precisely control how different molecules assemble into complex nanoscale materials that can improve human health, enable more efficient manufacturing, and drive future technological innovation. This research aims to provide kinetics and mechanistic insights into how different types of molecules recognize one another and assemble into predictable, well-organized architectures. In addition to developing new design principles that enable new materials from multicomponent assemblies, this research will apply these principles to create nanomaterials that prevent the harmful aggregation of proteins associated with diseases such as type 2 diabetes and Alzheimer’s disease. This project has the potential to accelerate innovation in biotechnology, support the development of new therapies and biomanufacturing technologies, and strengthen the growing U.S. bioeconomy. The project will also provide hands-on research experiences and mentoring for undergraduate students, helping them develop scientific skills, connect with research and internship opportunities, and prepare for careers that strengthen the nation’s future STEM workforce. By training the next generation of scientists and engineers while advancing fundamental materials research, this project will strengthen U.S. leadership in innovation, biotechnology, and the emerging bioeconomy. This project will establish fundamental design principles for the programmable self-assembly of multicomponent, supramolecular nanostructures with spatially organized, orthogonally sorted domains. A templated assembly strategy will be developed in which preassembled components direct hierarchical organization through orthogonal noncovalent interactions at supramolecular interfaces. The impact of hydrogen bonding, electrostatic, hydrophobic, and π-π interactions on self-sorting, intercomponent recognition, and assembly stability will be systematically examined to establish molecular design principles for multicomponent assembly. The generality of these principles will be evaluated in biologically relevant, non-engineered systems by targeting the aggregation of human islet amyloid polypeptide (hIAPP), a peptide implicated in type 2 diabetes. Because the ability to form amyloid fibrils is a common property of proteins despite substantial differences in sequence and structure, the design framework developed in this project will be applied to create assemblies that selectively recognize and bind amyloidogenic interfaces, thereby inhibiting pathological protein aggregation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.