{Reference Type}: Journal Article {Title}: Self-Powered Engineering of Cell Membrane Receptors to On-Demand Regulate Cellular Behaviors. {Author}: Geng H;Zhi S;Zhou X;Yan Y;Zhang G;Dai S;Lv S;Bi S; {Journal}: Nano Lett {Volume}: 24 {Issue}: 26 {Year}: 2024 Jul 3 {Factor}: 12.262 {DOI}: 10.1021/acs.nanolett.4c01080 {Abstract}: 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.