A self-templated route to monodisperse complex droplets as artificial extremophile-mimic from coacervate-liposome interplay

Bottom-up synthetic biology seeks to construct artificial cells from simple building blocks for exploring origin and principles of cellular life and material design. Although cellular life may have emerged spontaneously, programmable integration of building blocks into size, membrane property-controlled compartments (liposome or coacervate) towards cellular organization, without using specialized devices, has proven difficult. Here, we report a self-templated route to monodisperse complex droplets in bulk solution from coacervate-liposome synergy, with nanoliposome controlling coacervate size and coacervate templating on-surface nanoliposome fusion. Nanoliposome-coated monodisperse coacervates are self-assembled within 30 seconds, which are sealed by fusing nanoliposomes into size-controlled giant unilamellar vesicles (GUVs), with model building blocks combinatorially integrated into droplets. Defect-free membrane is established on coacervate, which render these complex GUVs surviving at extreme osmotic, salty and pH conditions (4 M NaCl, 100 mM HCl, 1 M NaOH), while providing homeostasis for enzymatic reactions, reminiscent of extremophiles. © The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved.