%0 Journal Article %T Self-Powered Engineering of Cell Membrane Receptors to On-Demand Regulate Cellular Behaviors. %A Geng H %A Zhi S %A Zhou X %A Yan Y %A Zhang G %A Dai S %A Lv S %A Bi S %J Nano Lett %V 24 %N 26 %D 2024 Jul 3 %M 38913401 %F 12.262 %R 10.1021/acs.nanolett.4c01080 %X On-demand engineering of cell membrane receptors to nongenetically intervene in cellular behaviors is still a challenge. Herein, a membraneless enzyme biofuel cell-based self-powered biosensor (EBFC-SPB) was developed for autonomously and precisely releasing Zn2+ to initiate DNAzyme-based reprogramming of cell membrane receptors, which further mediates signal transduction to regulate cellular behaviors. The critical component of EBFC-SPB is a hydrogel film on a biocathode which is prepared using a Fe3+-cross-linked alginate hydrogel film loaded with Zn2+ ions. In the working mode in the presence of glucose/O2, the hydrogel is decomposed due to the reduction of Fe3+ to Fe2+, accompanied by rapid release of Zn2+ to specifically activate a Zn2+-responsive DNAzyme nanodevice on the cell surface, leading to the dimerization of homologous or nonhomologous receptors to promote or inhibit cell proliferation and migration. This EBFC-SPB platform provides a powerful "sensing-actuating-treating" tool for chemically regulating cellular behaviors, which holds great promise in precision biomedicine.