The bioengineering applications of cells, such as cell
printing
and multicellular assembly, are directly limited by cell damage and
death due to a harsh environment. Improved cellular robustness thus
motivates investigations into cell encapsulation, which provides essential
protection. Here we target the cell-surface glycocalyx and cross-link
two layers of DNA nanorods on the cellular plasma membrane to form
a modular and programmable nanoshell. We show that the DNA origami
nanoshell modulates the biophysical properties of cell membranes by
enhancing the membrane stiffness and lowering the lipid fluidity.
The nanoshell also serves as armor to protect cells and improve their
viability against mechanical stress from osmotic imbalance, centrifugal
forces, and fluid shear stress. Moreover, it enables mediated cell–cell
interactions for effective and robust multicellular assembly. Our
results demonstrate the potential of the nanoshell, not only as a
cellular protection strategy but also as a platform for cell and cell
membrane manipulation.