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

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Non-Technical Summary

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 and ecological health. Nanoparticles that can recapitulate biological processes to sense analytes, such as a local chemical or protein, and respond via the synthesis and secretion of biomolecules, would dramatically improve the efficacy of biosensing applications.

Towards this goal, this NSF CAREER proposal, will design particles that incorporate stabilizing molecules alongside membrane proteins and protein synthesis systems. The project will map how the unique mechanical and physical properties of the particles designed impact the sensing capabilities and bioreactivity of the designed particles. The proposed research is expected to contribute a markedly improved biosensing platform that could generate improved sensitivity of biological detection and enhanced stability of cell-free systems, overcoming previous obstacles to their deployment as autonomous systems.

This advance will enable researchers and clinicians to detect biological molecules in an array of water-containing environments, from vasculature to ground water, allowing for the early detection of infection and disease to microbial content. The educational objective of this proposal will develop an educational program partnering with teachers from Chicago Public Schools (CPS).

This program will provide much-needed community engagement training and pedagogical skills for STEM graduate students, while providing important teacher-leader training and professional network building for public school elementary/middle grade teachers. Technical Summary

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 of hybrid membranes to incorporate membrane proteins, there is still a critical gap in the knowledge base that pertains to the effect of membrane biophysical properties on membrane protein and cell-free expression dynamics. These limitations in our understanding of the structure-function relationship of synthetic membranes 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.

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.