Abstract

DNA nanotechnology enables the construction of sophisticated biomimetic nanomachines that are increasingly central to the growing efforts of creating complex cell-like entities from the bottom-up. DNA nanostructures have been proposed as both structural and functional elements of these artificial cells, and in many instances are decorated with hydrophobic moieties to enable interfacing with synthetic lipid bilayers or regulating bulk self-organisation. In this feature article we review recent efforts to design biomimetic membrane-anchored DNA nanostructures capable of imparting complex functionalities to cell-like objects, such as regulated adhesion, tissue formation, communication and transport. We then discuss the ability of hydrophobic modifications to enable the self-assembly of DNA-based nanostructured frameworks with prescribed morphology and functionality, and explore the relevance of these novel materials for artificial cell science and beyond. Finally, we comment on the yet mostly unexpressed potential of amphiphilic DNA-nanotechnology as a complete toolbox for bottom-up synthetic biology – a figurative and literal scaffold upon which the next generation of synthetic cells could be built.

Highlights

  • Since its advent in the eighties 1, DNA nanotechnology has evolved from an inspiring concept to a practical toolkit driving advances in several areas of fundamental and applied science 2

  • While most approaches for establishing responsiveness in artificial lipid bilayers have relied on the reconstitution of protein-based machinery 69,72,73,92–94, the programmability afforded by DNA nanotechnology offers an increasingly popular alternative 2

  • The authors focused on the effect of DNA-linker density on the melting temperature of the self-assembled phases and observed, intriguingly, that no aggregation occurs below a critical coverage owing to the competition between intra-Large Unilamellar Vesicles (LUVs) loops and inter-LUV bridges 76

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Summary

Introduction

Among artificial molecular-scale devices, the sheer variety of architectures and responses demonstrated with nucleicacid nanostructures makes them comparable with biologically occurring machinery in terms of complexity and functionality 38–41. The biomimetic microrobots, often referred to as artificial cells, are constructed from inanimate molecular components to replicate emergent responses typically observed in biological cells, including energy conversion, communication, motion, adaptation and, yet unachieved, replication and evolution 44–46. In view of the ubiquitous presence of lipid interfaces, membrane-bound protein machinery is often featured in artificial cellular systems, regulating transport, adhesion and morphological responses 69–73 In this feature article we delve into several examples of synthetic DNA nanostructures designed to replicate the structure and functionality of biological molecular machinery in the context of cell mimicry, focusing in particular on bilayer-anchored devices acting as synthetic receptors mediating adhesion 74–80, tissue formation 74,81, communication 82 and membrane sculpting 83–87. DNA nanotechnology as a versatile and integrated toolkit to simultaneously prescribe structural and information processing aspects in synthetic cells, identify key outstanding challenges, and express our view on those functionalities that could have the greatest fundamental and technological impact

Programming biomimetic responses with membrane-associated DNA nanodevices
DNA receptors to regulate membrane adhesion and tissue formation
Bulk self-assembly of amphiphilic DNA nanostructures
Conclusive remarks and future challenges
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