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

Roger Rubio-Sánchez,Pietro Cicuta,Lorenzo Di Michele,Simone Eizagirre Barker,Michal Walczak

doi:10.1021/acs.nanolett.0c04867

Roger Rubio-Sánchez, Pietro Cicuta + Show 3 more

Open Access

https://doi.org/10.1021/acs.nanolett.0c04867

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Journal: Nano letters	Publication Date: Mar 18, 2021
Citations: 27	License type: CC BY 4.0

Affiliation: University of Cambridge, Imperial College London

Abstract

Cell membranes regulate the distribution of biological machinery between phase-separated lipid domains to facilitate key processes including signaling and transport, which are among the life-like functionalities that bottom-up synthetic biology aims to replicate in artificial-cellular systems. Here, we introduce a modular approach to program partitioning of amphiphilic DNA nanostructures in coexisting lipid domains. Exploiting the tendency of different hydrophobic “anchors” to enrich different phases, we modulate the lateral distribution of our devices by rationally combining hydrophobes and by changing nanostructure size and topology. We demonstrate the functionality of our strategy with a bioinspired DNA architecture, which dynamically undergoes ligand-induced reconfiguration to mediate cargo transport between domains via lateral redistribution. Our findings pave the way to next-generation biomimetic platforms for sensing, transduction, and communication in synthetic cellular systems.

Highlights

Cell membranes regulate the distribution of biological machinery between phase-separated lipid domains to facilitate key processes including signaling and transport, which are among the life-like functionalities that bottomup synthetic biology aims to replicate in artificial-cellular systems
Bottom-up synthetic biology aims at replicating functionalities typically associated with biological cells in microrobots designed de novo or “artificial cells”.16−18 Just like their biological counterparts, many artificial-cell designs rely on semipermeable membranes for their compartmentalization requirements,[19−21] which can be constructed from polymers[22] and proteopolymer systems,[23,24] colloids[25,26] and, more often, synthetic lipid bilayers.[21]
We demonstrate this effect with a nanostructure featuring both dC and single tocopherol (sT) anchoring modules, similar to that shown in Figure 3 but in which the fluorescent dsDNA linker module connecting the anchor duplexes can reversibly bind to or detach from either via toehold-mediated strand displacement,[61] a mechanism that is reminiscent of two-component biological receptors undergoing ligand-induced dimerization.[5,6]