Biological cells are complex machineries that are able to do many things that are still beyond the capabilities of engineering and science. Those capabilities can be used by preserving the cells in a protective shell before bringing them into a hostile environment, where the cell's functionalities are to be used. This proposal presents a new way to construct responsive coatings for cells, such as yeast and bacterial cells, using layer-by-layer (LbL) techniques to make polymeric capsules based on hydrogen bonding of the polymeric layers, particularly silk-based polymers. This proposed approach will bypass the known toxicity of past cationic (positively charged) LbL polymers, as well as resolve some of the issues with silica sol-gel and hydrogel encapsulation technologies. The encapsulation methodology described in this proposal, if successfully developed, could lead to a high impact on new ways to protect cells from their environments and thus enable cellular technologies in cell-based biosensing, cell-based therapies, and tissue engineering.
The proposed approach is systematic and well laid out, involving identification of components from which to fabricate the multilayers, studies of the transport properties of the multilayers, and then encapsulation of yeast and bacterial cells with the select polymers and investigation of protective effects of the shells on the cells as they are challenged in various environments. Novel aspects of the proposal include the use of shear and/or ionic strength changes into induce conformational changes (beta-sheet formation) in silk-based proteins to achieve physical cross-linking. The planned approach of using soft bio-interfaces that are robust, semipermeable, and cyto-friendly will help the investigators to reach their ultimate goal of gaining an understanding of interfacial organization, transport properties, and the mechanism of interactions between the shells and cell surfaces that are necessary to preserve the viability and function of genetically engineered microbial cells.
