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.
摘要：
对细胞膜受体进行按需工程化以进行非遗传干预细胞行为仍然是一个挑战。在这里，开发了基于无膜酶生物燃料电池的自供电生物传感器（EBFC-SPB），用于自主和精确地释放Zn2，以启动基于DNAzyme的细胞膜受体重编程，进而介导信号转导调节细胞行为。EBFC-SPB的关键成分是生物阴极上的水凝胶膜，该膜是使用负载有Zn2离子的Fe3交联的藻酸盐水凝胶膜制备的。在存在葡萄糖/O2的工作模式下，由于Fe3还原为Fe2，水凝胶分解，伴随着Zn2的快速释放，以特异性激活细胞表面上的Zn2响应性DNA酶纳米器件，导致同源或非同源受体的二聚化，以促进或抑制细胞增殖和迁移。这个EBFC-SPB平台提供了一个强大的“传感-驱动-处理”工具，用于化学调节细胞行为，这在精密生物医学领域有着巨大的前景。
