Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment

Abstract

Biology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. 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. We show that the corona can be selectively displaced with a molecular cue, exposing the ‘sticky’ core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria.

Self assembling cluster crystals from DNA based dendritic nanostructures

“…The tendency of particles to form stable clusters in the absence of attractions is a phenomenon clearly distinct from micellization, which is common for block copolymers in selective solvents 48 – 50 , polymeric amphiphiles 51 – 57 , and small molecule amphiphile surfactant sytems 58 . A conventional block-copolymer amphiphilie, a system most relevant to our DNA dendritic-based triblock, is commonly composed of a hydrophilic and a hydrophobic segment that are covalently linked.…”

“…A conventional block-copolymer amphiphilie, a system most relevant to our DNA dendritic-based triblock, is commonly composed of a hydrophilic and a hydrophobic segment that are covalently linked. The hydrophobic part can be a synthetic polymeric block 51 , 52 , 54 , 59 or different types of moieties (such as long-carbon alkyl chains, lipid molecule and fluorescent dyes) 53 , 55 , 57 . These amphiphiles can be assembled into micelles (aggregates) with rich morphological and size diversity at room temperature at low critical micelle concentration ( c m c ); with the latter obtained at extremely low concentrations, and in particular many orders of magnitude below the overlap concentration ( c * ) of amphiphiles in solution.…”

Amphiphilic DNA nanostructures for bottom-up synthetic biology

“… 176,177 To improve on this aspect, Walczak et al devised a strategy which enables the production of amphipilic DNA aggregates with sizes ranging from a few hundred nanometers to several microns. 178 Specifically, the authors adopted a two-step self-assembly protocol in which an initial rapid quench from high to intermediate temperature leads to C-Star aggregate nucleation and initial growth, and is followed by a second quench from intermediate to low temperature which triggers the passivation of the aggregates with a non-sticky (hydrophilic) DNA corona. The latter arrests the growth of the amphiphilic DNA aggregates, whose size can thus be programmed by tuning the incubation time at intermediate temperature.…”

“…The amphiphilic DNA frameworks reviewed in this section have been demonstrated to possess an array of unique features, including controllable porosity, 90 responsiveness to various molecular and environmental stimuli, 90,164 programmable aggregate size, 178 and triggered interactions with lipid membranes and living cells. 178 These characteristics make them potential candidates as both structural and functional elements in artificial cell implementations. As proposed and demonstrated in several instances, membrane-less compartments 64,65 represent an intriguing alternative to membrane-based enclosures to serve as scaffold for artificial cells.…”

Reaction-diffusion patterning of DNA-based artificial cells

“…Similar constructs were previously demonstrated to form nanoporus phases with programmable structure, molecular-sieving properties, stimuli responsiveness, and the ability to host dynamic DNA circuitry. 23–25,28,29 As depicted in Fig. 1B, Figure S1 (SI), and detailed in the Experimental Methods (SI), spherical aggregates with cell-like dimensions (10 - 40 μm in diameter) readily emerge from a one-pot annealing reaction.…”