Photoactivatable Materials for Versatile Single-Cell Patterning Based on the Photocaging of Cell-Anchoring Moieties through Lipid Self-Assembly

• Published in: Journal of the American Chemical Society Vol. 144; no. 29; pp. 13154 - 13162
• Main Authors: Yamahira, Shinya, Misawa, Ryuji, Kosaka, Takahiro, Tan, Mondong, Izuta, Shin, Yamashita, Hayato, Heike, Yuji, Okamoto, Akimitsu, Nagamune, Teruyuki, Yamaguchi, Satoshi
• Format: Journal Article
• Language: English
• Published: American Chemical Society 27.07.2022
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c02949

Versatile methods for patterning multiple types of cells with single-cell resolution have become an increasingly important technology for cell analysis, cell-based device construction, and tissue engineering. Here, we present a photoactivatable material based on poly­(ethylene glycol) (PEG)-lipids for patterning a variety of cells, regardless of their adhesion abilities. In this study, PEG-lipids bearing dual fatty acid chains were first shown to perfectly suppress cell anchoring on their coated substrate surfaces whereas those with single-chain lipids stably anchored cells through lipid–cell membrane interactions. From this finding, a PEG-lipid with one each of both normal and photocleavable fatty acid chains was synthesized as a material that could convert the chain number from two to one by exposure to light. On the photoconvertible PEG-lipid surface, cell anchoring was activated by light exposure. High-speed atomic force microscopy measurements revealed that this photocaging of the lipid–cell membrane interaction occurs because the hydrophobic dual chains self-assemble into nanoscale structures and cooperatively inhibit the anchoring. Light-induced dissociation of the lipid assembly achieved the light-guided fine patterning of multiple cells through local photoactivation of the anchoring interactions. Using this surface, human natural killer cells and leukemia cells could be positioned to interact one-by-one. The cytotoxic capacity of single immune cells was then monitored via microscopy, showing the proof-of-principle for applications in the high-throughput analysis of the heterogeneity in individual cell–cell communications. Thus, the substrate coated with our photoactivatable material can serve as a versatile platform for the accurate and rapid patterning of multiple-element cells for intercellular communication-based diagnostics.