Tailoring the appearance: what will synthetic cells look like?

Spoelstra, Willem Kasper; Deshpande, Siddharth; Dekker, Cees

doi:10.1016/j.copbio.2017.11.005

Cited by 91 publications

(83 citation statements)

References 73 publications

(94 reference statements)

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“…Construction of artificial or synthetic cells can lead to advances in understanding cell biology and in other fields such as biotechnology, medicine or materials science where inspiration from biology can be applied in new ways [1][2][3][4][5]. For the purposes of this review, we will use the terms 'artificial' and 'synthetic' interchangeably and consider only artificial cells produced from the bottomup, by combining biological or non-biological components to produce microscale assemblies that are meant to serve as mimics of one or more aspects of biological cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

Liquid–liquid phase separation in artificial cells

Crowe¹,

Keating²

2018

Interface Focus.

164

152

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Liquid–liquid phase separation (LLPS) in biology is a recently appreciated means of intracellular compartmentalization. Because the mechanisms driving phase separations are grounded in physical interactions, they can be recreated within less complex systems consisting of only a few simple components, to serve as artificial microcompartments. Within these simple systems, the effect of compartmentalization and microenvironments upon biological reactions and processes can be studied. This review will explore several approaches to incorporating LLPS as artificial cytoplasms and in artificial cells, including both segregative and associative phase separation.

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Section: Introductionmentioning

confidence: 99%

Liquid–liquid phase separation in artificial cells

Crowe¹,

Keating²

2018

Interface Focus.

164

152

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“…These characteristics of biological condensates make them versatile players in cells. Due to their unique properties, coacervates also provide ample opportunities outside the in vivo context of live cells, for example, as potential architectural scaffolds for assembling an artificial minimal cell, as an alternative to traditional membranous structures such as liposomes …”

Section: Introductionmentioning

confidence: 99%

FtsZ‐Induced Shape Transformation of Coacervates

et al. 2018

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Recently, both the cellular and synthetic biology communities have expressed a strong interest in coacervates, membrane‐less liquid droplets composed of densely packed multivalent molecules that form as a result of spontaneous phase separation. Here, it is studied how FtsZ, a protein that plays a key role in the bacterial division process, remodels coacervates made of polylysine (pLL) and guanosine triphosphate (GTP). It is shown that FtsZ strongly partitions at the surface of the coacervates and induces their disassembly due to the hydrolysis of GTP by FtsZ. Surprisingly, the coacervates are found to promote lateral interactions between FtsZ filaments, inducing the formation of an emanating network of FtsZ bundles that interconnect neighboring coacervates. Under mechanical stress, coacervates are shown to fracture, resulting in profound invaginations along their circumference. The results bring out the potential of coacervates for their use as membrane‐free scaffolds for building synthetic cells as well as are possibly relevant for coacervation in prokaryotic cells.

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“…It may, for example, be possible to use a comparable approach to create de novo selective molecular filters (e.g. for use in artificial cells 62,63 ), systems that would rely on selective partitioning of molecules in meshworks of unfolded proteins with assigned properties. Control can be asserted over the composition and geometry of the meshwork e.g.…”

Section: Discussionmentioning

confidence: 99%

A designer FG-Nup that reconstitutes the selective transport barrier of the Nuclear Pore Complex

Fragasso

Vries

Sluis

et al. 2020

Preprint

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Nuclear Pore Complexes (NPCs) regulate bidirectional transport between the nucleus and the cytoplasm. Intrinsically disordered FG-Nups line the NPC lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins freely pass. The mechanism underlying selective transport through the NPC is still debated. Here, we reconstitute the selective behaviour of the NPC bottom-up by introducing a rationally designed artificial FG-Nup that mimics natural Nups. Using QCM-D, we measure a strong affinity of the artificial FG-Nup brushes to the transport receptor Kap95, whereas no binding occurs to cytosolic proteins such as BSA. Solid-state nanopores with the artificial FG-Nups lining their inner walls support fast translocation of Kap95 while blocking BSA, thus demonstrating selectivity. Coarse-grained molecular dynamics simulations highlight the formation of a selective meshwork with densities comparable to native NPCs. Our findings show that simple design rules can recapitulate the selective behaviour of native FG-Nups and demonstrate that no specific spacer sequence nor a spatial segregation of different FG-motif types are needed to create functional NPCs. IntroductionNucleocytoplasmic transport is orchestrated by the Nuclear Pore Complex (NPC), which imparts a selective barrier to biomolecules 1,2 . The NPC is a large eightfold-symmetric protein complex (with a size of ~52 MDa in yeast and ~112 MDa in vertebrates) that is embedded within the nuclear envelope and comprises ~30 different types of Nucleoporins ('Nups') 3,4 . Intrinsically disordered proteins, termed FG-Nups, line the central channel of the NPC. FG-Nups are characterized by the presence of phenylalanine-glycine (FG) repeats separated by spacer sequences 5 and they are highly conserved throughout species 6 . FG-Nups carry out a dual function: By forming a dense barrier (100-200 mg/mL) within the NPC lumen, they allow passage of molecules in a size-selective manner 7-10 . Small molecules can freely diffuse through, whereas larger particles are generally excluded 11 . At the same time, FG-Nups mediate the transport of large NTR-bound (Nuclear Transport Receptor) cargoes across the NPC through transient hydrophobic interactions between FG repeats and hydrophobic pockets on the convex side of NTRs 12 . Various models have been developed in order to connect the physical properties of FG-Nups to the size-selective properties of the NPC central channel, e.g. the 'virtual-gate' 13 , 'selective phase' 14,15 , 'reduction of dimensionality' 16 , 'kap-centric' 17-19 , 'polymer brush' 20 , and 'forest' 5 models.As is evident from the multitude of transport models, no consensus on the NPC transport mechanisms has yet been reached.The NPC is highly complex in its architecture and dynamics, being constituted by many different Nups that simultaneously interact with multiple transiting cargoes and NTRs. In fact, translocating cargoes may amount to almost half of the mass of the central channel, so they may be considered an ...

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Tailoring the appearance: what will synthetic cells look like?

Cited by 91 publications

References 73 publications

Liquid–liquid phase separation in artificial cells

Liquid–liquid phase separation in artificial cells

FtsZ‐Induced Shape Transformation of Coacervates

A designer FG-Nup that reconstitutes the selective transport barrier of the Nuclear Pore Complex

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