Rubio-Sánchez, Roger

University of Cambridge (UK)


A Modular, Dynamic, DNA-based Platform for Regulating Cargo Distribution and Transport between Lipid Domains


Biological membranes feature highly evolved proteo-lipid machinery able to co-localise in lipid rafts, nano-scaled assemblies believed to underpin signal transduction [1], amongst other cellular processes. Bottom-up synthetic biology aims to replicate life-like behaviours in model artificial cells [2], often using synthetic lipid bilayers as passive enclosures that lack the functional complexity associated to their biological analogues. DNA nanotechnology has emerged as a popular choice for biomimicry, coupling bio-inspired nano-devices with model membranes using amphiphilic oligonucleotides [3]. In fact, amphiphilic DNA nanostructures also undergo partitioning in lipid domains [4], evoking the affinity of proteins for raft microenvironments.

Here, we regulate the lateral distribution of DNA nanostructures in phase-separated membranes by exploiting the tendency of cholesterol and tocopherol motifs to respectively enrich liquid-ordered (Lo) and liquid-disordered (Ld) domains. By prescribing combinations of multiple anchors, changes to nanostructure topology, and size, our DNA architectures are programmed to achieve partitioning states that span the energy landscape. In addition, the functionality of our approach is showcased with a responsive biomimetic DNA device that dynamically achieves ligand-induced reconfiguration and mediates cargo transport between lipid domains. Our synergistic platform [5] paves the way for the development of next-generation biomimetic DNA-based architectures, that can achieve sensing and communication in synthetic cellular systems


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