Self-Assembled Multifunctional Biointerfaces - Research in the Zha Lab at Rensselaer Polytechnic Institute focuses on creating biomimetic materials and processes that aid in studying, diagnosing, preventing, and treating disease. By leveraging the self-assembly capabilities of rationally designed biomacromolecules, this research aims to create hierarchically structured systems that are multifunctional. This MIRA R35 for Early Stage Investigators project will support the exploration and development of new approaches for enhancing the function of biomedical and biological interfaces. The approaches are based on an interfacial phenomenon recently reported by the PI, whereby robust nanothin coatings are generated non- covalently on surfaces by controlling the self-assembly of structural proteins such as silk fibroin. These coatings can transform the physicochemical properties of a wide range of substrates under biocompatible conditions, regardless of surface chemistry or topography and without specialized equipment. The research program will explore coatings that: i) exhibit dynamic behavior mimicking the temporal complexity of cell signaling in biological processes, ii) shield surfaces against unwanted macromolecular and cellular interactions, iii) improve biocompatibility and bioactivity of cell-material interfaces, and iv) present or release bioactive payloads in a sustained, controlled manner. While the innovations developed by the research program are disease-agnostic and will have the potential to address a wide range of biomedical challenges, three proof-of-concept topics using model systems will be examined in this project. 1) Coatings with temporally orchestrated release of multiple neurotrophic factors will be developed to control Schwann cell phenotype for nerve tissue regeneration. 2) Antifouling peptide motifs will be discovered by combinatorial synthesis and machine learning to generate coatings that improve the long-term performance of implanted biosensors. 3) Surfaces of living cells will be engineered by interfacial protein self- assembly to enhance their viability and bioactivity in therapeutic applications. The outcomes of this research program are expected to broadly yield versatile, modular tools for biomaterials development.
