Photocontrol of Non-Adherent Cell Adhesion via Azobenzene–PEG–Lipid/Cyclodextrin Host–Guest Interactions

Controlling cell attachment to substrates with spatiotemporal precision is a key technological foundation in fields such as tissue engineering, cell sorting, and cell-cell interaction analysis. Among existing approaches, azobenzene-based photocontrollable systems offer a promising strategy for the reversible regulation of cell adhesion. However, most conventional systems rely on the intrinsic adhesion capacity of adherent cells. Consequently, although the importance of non-adherent cell types has grown in biomedical research, their dynamic manipulation remains insufficiently explored. In this study, we developed a versatile system to control cell adhesion based on host-guest interactions between an azobenzene-lipid conjugate and a cyclodextrin-functionalized substrate. Using human chronic myelogenous leukemia (K562) cells, we successfully demonstrated photocontrolled adhesion and detachment, confirming the applicability of this system to non-adherent cells. Furthermore, we quantitatively measured the adhesion force and observed an inverse correlation between adhesion efficiency and adhesion force for different PEG linker lengths (2k, 4k, and 8k). This finding demonstrates the critical role of the linker length in effective cell surface modification. In conclusion, the proposed system establishes a photocontrollable adhesion method applicable to non-adherent cells, demonstrating its potential as a versatile technology for broad applications.