CAREER: Hybrid membranes as platforms for biomolecule detection, synthesis, and transport

Overview: The National Science Foundation has identified the need for advancements in biosensing in the fields of public health, food safety, agriculture, forensics, environmental protection, and homeland security. Vesicle-based systems that can recapitulate biological processes to sense analytes, such as a local chemical or protein, and perform signal processing behaviors to respond via the synthesis and secretion of biomolecules, would dramatically improve the efficacy of biosensing applications. Critical barriers toward realizing the design of a vesicle-based carrier that mimics these behaviors are (1) maintaining vesicle stability (2) enabling molecular recognition capabilities, and (3) coupling molecular recognition to cargo release. This NSF CAREER proposal, situated within the PI’s larger career goals, will address these barriers by rationally designing vesicles that incorporate stabilizing amphiphiles alongside membrane proteins and cell-free systems to surmount this obstacle. The research objective of this CAREER proposal is to provide in depth understanding of the unique mechanical and physical properties of hybrid vesicle membranes in relation to their effect on membrane protein dynamics and the activity of cell-free systems. The central hypothesis of this proposal is that hybrid vesicle membranes will enable the incorporation of functional membrane channels and activity of cell-free systems that together transduce biomolecule detection into a readable signal in complex fluids. These outcomes will, in turn, enable the detection of a range of biological molecules in complex fluids and treatment on onsite. Tightly integrated with my research objective is an educational objective to develop an educational program partnering with teachers from Chicago Public Schools (CPS) and provide community engagement training and pedagogical skills for STEM graduate students. Intellectual Merit: Hybrid membranes, assembled from diblock copolymers and phospholipids, have emerged as a potentially powerful material interface to design biosensors, drug delivery vehicles, and bioreactors. The chemical flexibility and stability that polymers impart to phospholipid membranes is complimented by the biological compatibility of phospholipids with membrane proteins. In spite of important recent demonstrations on the capacity to generate hybrid membranes that incorporate membrane proteins, there is still a critical gap in the knowledge base that pertains to the effect of membrane composition on membrane protein and cell-free expression dynamics. These limitations in our understanding of the structure-function relationship of synthetic membranes and the biological components they incorporate have seriously hampered the utility of synthetic vesicles as cellular mimetic biosensors. The proposed research is expected to contribute fundamental relationships between membrane composition, membrane physical properties, and the activity of embedded membrane proteins and encapsulated cell-free sensors. This contribution is significant because once we have established these material relationships, a new class of membrane-based devices can be designed that will provide a way to dynamically map chemical and environmental changes in vascular and aquatic environments that have been difficult to otherwise access. Broader Impacts. As agriculture and manufacturing expand globally and world-wide health crises continue to arise, the development of biosensors that allow improved molecular detection in a variety of settings are critical for our ability to maintain human a