ATP-Triggered In Situ Assembly of a Spider-Web-like DNA Nanoweb for Spatial Monitoring and Regulation of Membrane Receptor Dynamics.

Precise spatial interrogation of membrane receptor organization in living cells remains analytically challenging due to the lack of programmable interfaces capable of simultaneous signal amplification and spatially confined regulation. Here, we present a biomimetic ATP-responsive DNA nanoweb that assembles in situ on tumor cell membranes for quantitative fluorescent interrogation of receptor organization. Elevated ATP triggers catalytic hairpin assembly, generating a "molecular web" that directly interfaces with the plasma membrane. The nanoweb sterically blocks hepatocyte growth factor-induced C-Met dimerization and disrupts downstream pro-migratory signaling. Simultaneously, its dense DNA mesh introduces membrane-level physical constraints that restrain structural changes associated with motility. Through the concurrent modulation of signaling pathways and membrane mechanics, this nanoweb effectively suppresses migratory plasticity and invasive escape behaviors. The nanoweb exhibits high structural stability, enabling sustained modulation of metastatic behaviors while providing a built-in fluorescent activation readout. This work establishes a programmable DNA-based membrane interface for spatial analysis and precise regulation of receptor organization and provides a generalizable framework for engineering cell-surface analytical platforms.