Mimicking cellular compartmentalization in a hierarchical protocell through spontaneous spatial organization

Alexander F. Mason, Amy Yewdall, Pascal L.W. Welzen, Jingxin Shao, Marleen van Stevendaal, Jan C.M. van Hest (Corresponding author), David S. Williams (Corresponding author), Loai K.E.A. Abdelmohsen (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo.

LanguageEnglish
Pages1360-1365
Number of pages6
JournalACS Central Science
Volume5
Issue number8
DOIs
StatePublished - 28 Aug 2019

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Terpolymers
Cell membranes
Encapsulation
Cell culture
Self assembly
Culture Media
Enzymes
Robust stability

Cite this

@article{b1ef46a1b38342a9a3592e2880ccc6d5,
title = "Mimicking cellular compartmentalization in a hierarchical protocell through spontaneous spatial organization",
abstract = "A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo.",
author = "Mason, {Alexander F.} and Amy Yewdall and Welzen, {Pascal L.W.} and Jingxin Shao and {van Stevendaal}, Marleen and {van Hest}, {Jan C.M.} and Williams, {David S.} and Abdelmohsen, {Loai K.E.A.}",
year = "2019",
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T1 - Mimicking cellular compartmentalization in a hierarchical protocell through spontaneous spatial organization

AU - Mason,Alexander F.

AU - Yewdall,Amy

AU - Welzen,Pascal L.W.

AU - Shao,Jingxin

AU - van Stevendaal,Marleen

AU - van Hest,Jan C.M.

AU - Williams,David S.

AU - Abdelmohsen,Loai K.E.A.

PY - 2019/8/28

Y1 - 2019/8/28

N2 - A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo.

AB - A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo.

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