Synthetic Biology: Bottom-Up Assembly of Molecular Systems

Hirschi, Stephan; Ward, Thomas R.; Meier, Wolfgang; Müller, Daniel J.; Fotiadis, Dimitrios

doi:10.1021/acs.chemrev.2c00339

Cited by 56 publications

(43 citation statements)

References 446 publications

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“…The assembly of FtsZ macrostructures promoted by ZapD may also open new horizons for the biochemical reconstitution of contractile division engines in cell-like test tubes [109][110][111] in the framework of bottom-up synthetic biology 112,113 . Our preliminary results show that crosslinking of filaments by ZapD promoted the formation of dynamic FtsZ bundles within lipid vesicles that disassembled over time (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Crosslinking by ZapD drives the assembly of short FtsZ filaments into toroidal structures in solution

Merino‐Salomón

Schneider

Babl

et al. 2023

Preprint

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In most bacteria, division depends on a cytoskeletal structure, the FtsZ ring, that functions as a scaffold to recruit additional proteins, with which it forms the machinery responsible for division, the divisome. The detailed architecture of the ring, in particular the mechanisms of assembly, stabilization, and disassembly, are still largely unknown. Here, we highlight the role of FtsZ-associated proteins (Zaps) that stabilize the FtsZ ring by crosslinking the filaments. Among Zap proteins, ZapD binds the C-terminal domain of FtsZ, which serves as a hub for its regulation. We demonstrate that ZapD crosslinks FtsZ filaments into ring-like structures formed by a discontinuous arrangement of short filaments. Using cryo-electron tomography combined with biochemical analysis, we reveal the three-dimensional organization of the ring-like structures and shed light on the mechanism of FtsZ filament crosslinking by ZapD. Together, our data provide a model of how FtsZ-associated proteins can stabilize FtsZ filaments into discontinuous ring-like structures reminiscent of that existing in the bacterial cell.

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Section: Discussionmentioning

confidence: 99%

Crosslinking by ZapD drives the assembly of short FtsZ filaments into toroidal structures in solution

Merino‐Salomón

Schneider

Babl

et al. 2023

Preprint

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“…Black dashed arrows represent the inflow of ingredients through the membrane, and the blue dashed arrow indicates the incorporation of synthesised lipids into the membrane. Such simplified chemical schemes have been also proposed by others [2][3][4] . b Chemical scheme of the artificial metabolic pathways of our synthetic minimal cell consisting of three elementary units; energy production (orange), synthesis of information polymer (green), and membrane growth (blue).…”

mentioning

confidence: 91%

“…The synthesised lipid molecules are incorporated into the cell membrane, which results in membrane growth and division, i.e., proliferation. Fig 1a is also a representation of Gánti's chemoton model of living systems [3][4][5] . A living system requires recursive compartment proliferation by regulating compartment membrane area growth, compartment volume growth, as well as compartment deformation, and division processes.…”

mentioning

confidence: 99%

Synthesising a minimal cell with artificial metabolic pathways

et al. 2023

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A “synthetic minimal cell” is considered here as a cell-like artificial vesicle reproduction system in which a chemical and physico-chemical transformation network is regulated by information polymers. Here we synthesise such a minimal cell consisting of three units: energy production, information polymer synthesis, and vesicle reproduction. Supplied ingredients are converted to energy currencies which trigger the synthesis of an information polymer, where the vesicle membrane plays the role of a template. The information polymer promotes membrane growth. By tuning the membrane composition and permeability to osmolytes, the growing vesicles show recursive reproduction over several generations. Our “synthetic minimal cell” greatly simplifies the scheme of contemporary living cells while keeping their essence. The chemical pathways and the vesicle reproduction pathways are well described by kinetic equations and by applying the membrane elasticity model, respectively. This study provides new insights to better understand the differences and similarities between non-living forms of matter and life.

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“…Model membrane systems, like liposomes, lamellar liquid crystals, supported lipid bilayers and Langmuir monolayers, have been extremely relevant for fundamental studies related to the physiological and biophysical properties of biological membranes [ 1 , 2 , 3 ]. They have also become very useful in terms of biomedical and pharmaceutical applications, chief among them the development of efficient nanocarriers for bioactive molecules [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Model Catanionic Vesicles from Biomimetic Serine-Based Surfactants: Effect of the Combination of Chain Lengths on Vesicle Properties and Vesicle-to-Micelle Transition

et al. 2023

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Mixtures of cationic and anionic surfactants often originate bilayer structures, such as vesicles and lamellar liquid crystals, that can be explored as model membranes for fundamental studies or as drug and gene nanocarriers. Here, we investigated the aggregation properties of two catanionic mixtures containing biomimetic surfactants derived from serine. The mixtures are designated as 12Ser/8-8Ser and 14Ser/10-10Ser, where mSer is a cationic, single-chained surfactant and n-nSer is an anionic, double-chained one (m and n being the C atoms in the alkyl chains). Our goal was to investigate the effects of total chain length and chain length asymmetry of the catanionic pair on the formation of catanionic vesicles, the vesicle properties and the vesicle/micelle transitions. Ocular observations, surface tension measurements, video-enhanced light microscopy, cryogenic scanning electron microscopy, dynamic and electrophoretic light scattering were used to monitor the self-assembly process and the aggregate properties. Catanionic vesicles were indeed found in both systems for molar fractions of cationic surfactant ≥0.40, always possessing positive zeta potentials (ζ = +35–50 mV), even for equimolar sample compositions. Furthermore, the 14Ser/10-10Ser vesicles were only found as single aggregates (i.e., without coexisting micelles) in a very narrow compositional range and as a bimodal population (average diameters of 80 and 300 nm). In contrast, the 12Ser/8-8Ser vesicles were found for a wider sample compositional range and as unimodal or bimodal populations, depending on the mixing ratio. The aggregate size, pH and zeta potential of the mixtures were further investigated. The unimodal 12Ser/8-8Ser vesicles (<DH> ≈ 250 nm, pH ≈ 7–8, ζ ≈ +32 mV and a cationic/anionic molar ratio of ≈2:1) are particularly promising for application as drug/gene nanocarriers. Both chain length asymmetry and total length play a key role in the aggregation features of the two systems. Molecular insights are provided by the main findings.

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Synthetic Biology: Bottom-Up Assembly of Molecular Systems

Cited by 56 publications

References 446 publications

Crosslinking by ZapD drives the assembly of short FtsZ filaments into toroidal structures in solution

Crosslinking by ZapD drives the assembly of short FtsZ filaments into toroidal structures in solution

Synthesising a minimal cell with artificial metabolic pathways

Model Catanionic Vesicles from Biomimetic Serine-Based Surfactants: Effect of the Combination of Chain Lengths on Vesicle Properties and Vesicle-to-Micelle Transition

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