4.8 Article

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

Journal

NANO LETTERS
Volume 21, Issue 7, Pages 2800-2808

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c04867

Keywords

DNA nanotechnology; lipid phase separation; lipid domains; partitioning; artificial cells; synthetic membranes; biomimicry

Funding

  1. Mexican National Council for Science and Technology (CONACYT) [472427]
  2. Cambridge Trust
  3. EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC) [EP/L015978/1, EP/S022953/1]
  4. Royal Society University Research Fellowship [UF160152]
  5. European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme (ERC-STG) [851667]
  6. European Research Council (ERC) [851667] Funding Source: European Research Council (ERC)

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This study introduces a modular approach to program the distribution of amphiphilic DNA nanostructures in lipid domains, enabling the regulation of biological machinery distribution. By exploiting different hydrophobic anchors to enrich different lipid phases, researchers were able to modulate the lateral distribution of devices by combining hydrophobes and adjusting nanostructure size and topology.
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.

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