Self-Powered Engineering of Cell Membrane Receptors to On-Demand Regulate Cellular Behaviors

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.