CAREER: Phase-separating Membrane Materials for Efficient and Specific Molecular Delivery to Cells

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Non-technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Austin is to develop biomaterials for drug delivery system. From eliminating cancerous tumors to repairing damaged tissues, medicine frequently relies on our ability to direct multiple types of therapeutics to diseased cells, while sparing healthy cells from exposure. This project designs biomaterials that are capable of precisely recognizing diseased cells and efficiently delivering therapeutics to them. In particular, the materials developed in this work undergo a dramatic transformation from a non-interactive state to a highly interactive state when they recognize specific markers on the surfaces of diseased cells. This strategy will enable highly specific therapeutic delivery to diseased cells, increasing the capability and efficiency of pharmaceutical therapy while decreasing side effects. Furthermore, this work will create new opportunities to build a broad range of simple, man-made materials and systems that mimic the ability of living cells to sense and respond to changes in their environment. As part of the broader impact activities, this project plans to increase minority student participation in STEM, by inviting a diverse group of freshman students to contribute original ideas for the design of minimal 'cell-like' systems. Several students with promising ideas will be invited to try them out in the laboratory, providing them with a unique opportunity to solve real-world problems by combining creativity with critical thinking. By presenting the results of these design projects to local high school science classes, students will build confidence in their ability to succeed in STEM, while simultaneously inspiring the next generation of students to consider STEM careers.Technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Austin is to develop biomaterials for drug delivery system to transport large macromolecular cargos such as genes and proteins efficiently and specifically across the cell's plasma membrane. In this project, the investigator will be mimicking a strategy used by cells to recognize one another -coupling of ligand-receptor binding to membrane biomaterials that phase separate when they recognize threshold levels of receptors on the surfaces of target cells. This award is cofunded by the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. This project will be addressing some of the challenges facing the drug delivery system of large macromolecular cargos efficiently and specifically to inside of the cell. This project will design and synthesize membrane-based biomaterials using synthetic and phase separating liposomes. Synthetic polysomes will be designed with careful tuning the density of ternary lipid mixture ligands and fusion proteins on its surface. During cell-cell recognition and fusion, ligand-receptor interactions alter the local membrane composition, causing cellular membranes to undergo a highly localized phase separation that dramatically concentrates ligands and receptors, strengthening cell-cell contacts. Following these contacts, these membrane biomaterials phase separate when they recognize threshold levels of receptors on the surfaces of target cells, driving membrane fusion and delivery of molecular cargos to the cellular cytoplasm. Furthermore, these materials provide new tools for designing 'cell-like' systems that sense and respond to environmental changes. Drawing on this toolkit, educational efforts will center on a new course that will challenge freshman in non-STEM majors to come up with ideas for 'simple biological machines'. This unique project will invite a diverse group of students to share in the excitement of scientific innovation while many are still choosing their academic major and future career, broadening participation in science on our campus.