Bottom-Up Assembly of Functional Intracellular Synthetic Organelles by Droplet-Based Microfluidics

Oskar Staufer*, Martin Schröter, Ilia Platzman, Joachim P. Spatz

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)

Abstract

Bottom-up synthetic biology has directed most efforts toward the construction of artificial compartmentalized systems that recreate living cell functions in their mechanical, morphological, or metabolic characteristics. However, bottom-up synthetic biology also offers great potential to study subcellular structures like organelles. Because of their intricate and complex structure, these key elements of eukaryotic life forms remain poorly understood. Here, the controlled assembly of lipid enclosed, organelle-like architectures is explored by droplet-based microfluidics. Three types of giant unilamellar vesicles (GUVs)-based synthetic organelles (SOs) functioning within natural living cells are procedured: (A) synthetic peroxisomes supporting cellular stress-management, mimicking an organelle innate to the host cell by using analogous enzymatic modules; (B) synthetic endoplasmic reticulum (ER) as intracellular light-responsive calcium stores involved in intercellular calcium signalling, mimicking an organelle innate to the host cell but utilizing a fundamentally different mechanism; and (C) synthetic magnetosomes providing eukaryotic cells with a magnetotactic sense, mimicking an organelle that is not natural to the host cell but transplanting its functionality from other branches of the phylogenetic tree. Microfluidic assembly of functional SOs paves the way for high-throughput generation of versatile intracellular structures implantable into living cells. This in-droplet SO design may support or expand cellular functionalities in translational nanomedicine.

Original languageEnglish
Article number1906424
JournalSmall
Volume16
Issue number27
DOIs
Publication statusPublished - 1 Jul 2020

Bibliographical note

Funding Information:
The authors would like to acknowledge funding from the Federal Ministry of Education and Research of Germany, Grant Agreement no. 13XP5073A, PolyAntiBak and the MaxSynBio Consortium, which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. They further acknowledge support from the Volkswagen Stiftung (priority call ?Life??). The authors are grateful to Andrea Hellwig (Interdisciplinary Centre for Neurosciences Heidelberg) for technical assistance during TEM preparation and imaging, Prof. Hilmar Bading (Interdisciplinary Centre for Neurosciences Heidelberg) for providing the opportunity to perform TEM work in his laboratory, as well as Elisa D'Este, Clara-Marie G?rth and Jasmine Hubrich (Max Planck Institute for Medical Research) for providing primary hippocampal neurons. O.S. acknowledges support from the Heidelberg Biosciences International Graduate School. O.S. is the Meurer Visiting Professor at the University of Bristol. J.P.S. is the Weston Visiting Professor at the Weizmann Institute of Science and part of the excellence cluster CellNetworks at the University of Heidelberg. The Max Planck Society is appreciated for its general support.

Funding Information:
The authors would like to acknowledge funding from the Federal Ministry of Education and Research of Germany, Grant Agreement no. 13XP5073A, PolyAntiBak and the MaxSynBio Consortium, which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. They further acknowledge support from the Volkswagen Stiftung (priority call “Life?”). The authors are grateful to Andrea Hellwig (Interdisciplinary Centre for Neurosciences Heidelberg) for technical assistance during TEM preparation and imaging, Prof. Hilmar Bading (Interdisciplinary Centre for Neurosciences Heidelberg) for providing the opportunity to perform TEM work in his laboratory, as well as Elisa D'Este, Clara‐Marie Gürth and Jasmine Hubrich (Max Planck Institute for Medical Research) for providing primary hippocampal neurons. O.S. acknowledges support from the Heidelberg Biosciences International Graduate School. O.S. is the Meurer Visiting Professor at the University of Bristol. J.P.S. is the Weston Visiting Professor at the Weizmann Institute of Science and part of the excellence cluster CellNetworks at the University of Heidelberg. The Max Planck Society is appreciated for its general support.

Publisher Copyright:
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • bottom-up synthetic biology
  • droplet-based microfluidics
  • giant unilamellar vesicles
  • synthetic organelles
  • translational nanomedicine

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