Encapsulation of single vesicles and single cells in a crosslinked microgel cage

Cell encapsulation provides an efficient strategy to enhance cell durability against harsh external conditions, that offers new possibilities for single-cell applications, such as, tissue engineering and regenerative medicine. Cell encapsulations in hydrogels is developed through various approaches. Still, it remains challenging to achieve single-cell encapsulation where the individual cells are surrounded by a hydrogel layer of well-defined thickness. In this study, temperature-responsive poly(N-isopropylacrylamide)-co-allylamine microgel particles are first assembled into a monolayer at the surface of giant unilamellar lipid vesicles and then inter-microgel crosslinked leading to single-vesicle encapsulation with a pre-defined hydrogel thickness. The same strategy is then extended to yeast cells. The successful encapsulation process is evidenced by the response of the encapsulated lipid vesicles/cells to osmotic gradient, the addition of detergent or salt, as well as changes in temperature. Moreover, cell viability tests show that the hydrogel cage can efficiently protect the cell against external harsh conditions, including elevated temperature, ultraviolet irradiation and osmotic stress. Furthermore, it is demonstrated that the microgel adsorption and interfacial assembly are significantly affected by membrane charge and structural heterogeneity of cell membrane, providing insight into rational design of single-cell encapsulation approach by regulating microgel adsorption on cell membranes with complex composition.