Morphology remodelling and membrane channel formation in synthetic cells via reconfigurable DNA nanorafts
The shape of biological matter is central to cell function at different length scales and determines how cellular components recognize, interact and respond to one another. However, their shapes are often transient and hard to reprogramme. Here we construct a synthetic cell model composed of signal-responsive DNA nanorafts, biogenic pores and giant unilamellar vesicles (GUVs). We demonstrate that reshaping of DNA rafts at the nanoscale can be coupled to reshaping of GUVs at the microscale. The nanorafts collectively undergo reversible transitions between isotropic and short-range local order on the lipid membrane, programmably remodelling the GUV shape. Assisted by the biogenic pores, during GUV shape recovery the locally ordered DNA rafts perforate the membrane, forming sealable synthetic channels for large cargo transport. Our work outlines a versatile platform for interfacing reconfigurable DNA nanostructures with synthetic cells, expanding the potential of DNA nanotechnology in synthetic biology.
The plasma membrane defines the physical boundary of a cell, separating the cytoplasmic components of the cell from the external environment. It comprises primarily lipids and proteins. While the physical nature of lipids forms the basis of membrane flexibility, membrane proteins sustain the cell’s chemical climate by assisting the transfer of molecules across the membrane1. In addition, both lipids and proteins are responsible for the cell’s morphology and distinct changes in membrane shape2,3,4,5. The exquisitely coordinated interplay between membrane shape and the function of membrane proteins has been of great scientific and technological interest6,7,8. To understand cells, the bottom-up approach in synthetic biology follows the ‘understanding by building’ route to construct artificial mimics de novo9,10,11,12,13, which capture the essence of their biological counterparts. DNA has proven to be an ideal construction material in this field14 due to its sequence-specific and predictable interactions following Watson–Crick base pairing15,16. Crescent-shaped DNA origami structures17 have been created to mimic BAR domain proteins18 to remodel the cell surface landscape by imprinting their curved shapes onto membranes. Tension-loaded DNA clamps, inspired by proteins such as ESCRT-III and dynamin, have been developed to drive membrane tubulation19. Besides membrane sculpting20,21,22,23,24,25, great efforts have also been devoted to construct channel protein mimics made of DNA that possess a large pore size or a nanomechanical lid for controlled molecular transport across lipid membranes26,27,28,29,30,31,32,33.
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