Transglutaminase-Catalyzed Encapsulation of Individual Mammalian Cells with Biocompatible and Cytoprotective Gelatin Nanoshells

Mammalian cells are extremely vulnerable to external assaults compared with plant and microbial cells because of the weakness of cell membranes compared with cell walls. Construction of ultrathin and robust artificial shells on mammalian cells with biocompatible materials is a promising strategy for protecting single cells against harsh environmental conditions. Herein, layer-by-layer assembly combined with a transglutaminase-catalyzed cross-linking reaction was employed to prepare cross-linked and biocompatible gelatin nanoshells on individual human cervical carcinoma cell line (HeLa) cells and mouse insulinoma cell line 6 (MIN6) cells. The encapsulated HeLa and MIN6 cells showed high viability and a prolonged encapsulation period. Moreover, the nanoshells can protect encapsulated cells from cytotoxic enzymes (such as trypsin) and polycation (polyethylenimine) attacks and help cells resist high physical stress. We also investigated how nanoshells would affect the cell viability, proliferation, and cell cycle distribution of encapsulated and released cells. The approach presented here may provide a new and versatile method for nanoencapsulation of individual mammalian cells, which would help cells endure various environmental stresses and thereby expand the application field of isolated mammalian cells.