Synthetic cell armor made of DNA origami

Therapeutic and bioengineering applications of cells, such as cell printing and cell delivery, are directly limited by cell damage and death due to harsh mechanical conditions. Improved cellular robustness thus motivates investigations into cell encapsulation that provides essential protection. Here we target the cell-surface glycocalyx and crosslink two layers of DNA origami nanorods on the cellular plasma membrane to form a nanoscale protective shell. This modular and programmable approach enables fine control over the layering and composition of membrane-deposited nanorods. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing membrane stiffness and lowering lipid fluidity. Moreover, the nanoshell serves as armor, protecting cells, limiting swelling and ultimately improving their viability against mechanical stress from osmotic imbalance and centrifugal forces. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy, but also as a platform for manipulating and studying plasma membrane mechanics.