Grafting-from Ring-Opening Metathesis Polymerization to Modify Cell Surfaces

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Non-Technical Summary: Cells are the smallest component of life. They have been engineered to be useful in areas such as medicine and energy. Cells can be used to produce critical therapies that can combat cancer, or the cells themselves can even be used as the medicine. Biologists are very good at engineering the internal processes that happen within the cell. It is much more difficult to precisely control what happens on the exterior of the cell. This leads to challenges that may limit the production of what the cells were engineered to make. It may also cause cell medicines to target and destroy healthy tissue. This project aims to develop a new way to attach synthetic materials to the surface of cells, This is important for advancing cell-based technologies because it will enable precise control of how cells interact with their external environment. One solution is to add polymers to the cell surface, creating hybrid materials that combine the cell and polymer. However, the tools to do this efficiently are still lacking. This project will focus on a chemical process called Ring-Opening Metathesis Polymerization to create these hybrid materials. The project will develop methods for attaching polymers to cells and create a toolkit for labeling cell surfaces. The project will also study how this labeling affects cell health, label longevity, and potential internal cell changes. The outcomes could benefit fields like healthcare, energy, and sensors. Finally, the project will provide undergraduate transfer students access to research activities, helping improve their academic and career outcomes. Technical Summary: The objective of this project is to develop grafting-from synthetic techniques from the surface of cells using ring-opening metathesis polymerization (ROMP). Cell-based biotechnology is an exploding field with impact in medicine, biosynthesis, sensor design, among many others. However, several limitations remain for cellular technology to be fully maximized. One critical challenge is manipulating the cell-surface to improve on various functional aspects such as diminishing biofouling, improving upon cell targeting in therapeutics, and immobilizing cells for continuous biosynthesis. One way to enable these capabilities is the introduction of polymers onto the cell surface to generate cell/polymer hybrid materials (CPHs). In the CPH realm, very little work has been done to develop the synthetic toolkit to enable the complex polymer chemistry necessary to enhance these capabilities. The work in this project will enable ROMP chemistry directly from the surface of a cell. This project will develop a basic framework to graft norbornene and oxanorbornene monomers directly from cell surfaces that will be broadly applicable to all CPH materials. The project will study macroinitiator composition and catalyst complexes to synthesize complex CPHs that are narrowly dispersed and living. Once catalysts are optimized, the project will develop a toolkit for labeling any cell by performing covalent modification of proteins, membrane insertion, and glycol-anchoring. Finally, the project will evaluate the long-term health, labeling longevity, and potential biochemical pathways associated with labeling. Cell-based technologies are an emerging field with uses in nearly every aspect of biotechnology and the nascent field of CPH materials would greatly impact all areas. This technology will have broad reach into all sectors of the public consciousness, including health care, alternative energy, and long-lasting sensors. Furthermore, the project will support training and mentoring of multiple transfer students at varying levels of engagement. We anticipate impacting ~30 transfer students per year in the Polymer Scientist for a Day/Week/Year modules, hereby positively impacting transfer student capital and improving academic outcomes for this often-neglected population. 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.