Here we demonstrate the design of responsive, DNA-based particles capable of permeabilizing and disrupting model lipid membranes when triggered by a molecular cue. Trans-membrane DNA constructs can mimic biological pores 25, 26 and simple enzymes 27, while membrane-adhering DNA-origami have been shown to establish local membrane curvature 28, 29. Simple amphiphilic DNA nanostructures have been utilized to engineer membrane adhesion and the formation of artificial tissues in both synthetic membranes 20, 21, 22, 23 and cells 24. DNA nanotechnology, with its yet unparalleled ability to construct nanoscale motifs of near-arbitrary shape and responsiveness, offers an ideal toolkit for mimicking the complex responses of membrane-active biological machinery 18, 19. In view of this applicative potential, efforts have been devoted to engineering natural membrane-sculpting entities 15, 17, and even mimic their responses with purely synthetic analogues. Notable examples include the routine adoption of α-hemolysin and other nanopore-forming proteins in single-molecule sensing and nucleic-acid sequencing 14, 15, and membrane-piercing antimicrobial peptides 16. The action of membrane-destabilizing biological agents is central to several biosensing, diagnostic, therapeutic, and synthetic-biological platforms. In other cases, membrane manipulation is associated with pathology, for instance in the action of viruses and parasites hijacking membrane-trafficking machinery to enter/leave cells 10, 11, pore-forming toxins permeabilizing membranes 12, and neurotoxic protein aggregates 13. Some of these agents are central to physiological processes 1, including protein channels mediating molecular transport 2, 3, enzymes dynamically regulating lipid composition and distribution 4, 5, and protein complexes that establish local membrane curvature to promote endo/exocytosis or cell division 6, 7, 8, 9. Several biomolecular agents, from small molecules to large protein complexes, have evolved the ability to sculpt lipid membranes changing their morphology, chemical composition, and physical properties. Proteolipid membranes represent the main means through which biological cells sustain chemical heterogeneity at the micro- and nanoscale, enabling most of their astounding responses. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. We show that the corona can be selectively displaced with a molecular cue, exposing the ‘sticky’ core. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds.