The Rise of the Nested Multicompartment Model in Synthetic Cell Research

Altamura, Emiliano; Albanese, Paola; Mavelli, Fabio; Stano, Pasquale

doi:10.3389/fmolb.2021.750576

Cited by 17 publications

(21 citation statements)

References 47 publications

(40 reference statements)

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“…The presence of organelles, and hence the concept of compartmentalization, enables the co-existence of chemically distinct reactions in spatially confined reactors while allowing multistep reactions and sustaining chemical gradients. The construction of a compartmentalized system in synthetic eukaryotes is thus key in order to build more sophisticated synthetic cells for both fundamental biological investigations, and as promising novel biomaterial for healthcare applications. − …”

Section: Introductionmentioning

confidence: 99%

pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells

et al. 2021

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By using electrostatic interactions as driving force to assemble vesicles, the droplet-stabilized method was recently applied to reconstitute and encapsulate proteins, or compartments, inside giant unilamellar vesicles (GUVs) to act as minimal synthetic cells. However, the droplet-stabilized approach exhibits low production efficiency associated with the troublesome release of the GUVs from the stabilized droplets, corresponding to a major hurdle for the droplet-stabilized approach. Herein, we report the use of pH as a potential trigger to self-assemble droplet-stabilized GUVs (dsGUVs) by either bulk or droplet-based microfluidics. Moreover, pH enables the generation of compartmentalized GUVs with flexibility and robustness. By co-encapsulating pH-sensitive small unilamellar vesicles (SUVs), negatively charged SUVs, and/or proteins, we show that acidification of the droplets efficiently produces dsGUVs while sequestrating the co-encapsulated material. Most importantly, the pH-mediated assembly of dsGUVs significantly improves the production efficiency of free-standing GUVs (i.e., released from the stabilizing-droplets) compared to its previous implementation.

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Section: Introductionmentioning

confidence: 99%

pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells

et al. 2021

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“…From the architectural viewpoint, complexification can be achieved via multiple compartmentalization. The latter can be hierarchical, i.e., according to a nested design (Altamura et al, 2021), or referred to 2D or 3D tissue-like systems (Bayley et al, 2019;Dupin et al, 2022): in both cases the behavior of the resulting "whole" will depend on the number, type, and function of constituent compartments.…”

Section: The Theoretical Track: What Scs Actually Arementioning

confidence: 99%

A four-track perspective for bottom-up synthetic cells

Stano

2022

Front. Bioeng. Biotechnol.

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A crucial move for the development of the bottom-up synthetic biology (SB) branch took place about 20 years ago, when Jack W. Szostak, David Bartel and Pier Luigi Luisi coauthored a Nature paper entitled "Synthesizing Life" (Szostak et al., 2001), which can be considered a sort of foundational paper for (or even the manifesto of) the modern approaches for constructing living artificial cells from scratch. Possibly as a sign of the Zeitgeist, the article was published almost simultaneously to two other foundational papers in SB (Elowitz et al., 2000;Gardner et al., 2000).The very idea of synthesizing life-the Faustian dream of all times-is not new. Several (unsuccessful) attempts to build cell-like systems of minimal complexity fill the annals of science (Hanczyc, 2009). These attempts share a common anti-vitalistic viewpoint: synthesizing (cellular) life from scratch should be possible, and it would demonstrate that the biological phenomenology follows a "continuity principle" with respect to physics and chemistry. That is, life is an emergent property of some molecular systems characterized by a very peculiar type of structural and dynamical (self-) organization. However trivial and generally taken for granted by scientists, the emergence of life from inanimate matter has never been demonstrated experimentally and it is still one of the big targets in science.What is, then, the remarkable and novel element that has been put forward in the "Synthesizing Life" article, and that can be considered as a foundational concept for bottom-up approaches in SB? The Authors actually focused on the hypothetical construction of primitive cell (protocell) models, made of catalytically active RNAs (ribozymes) (Bartel and Szostak, 1993; Eckland et al., 1995), encapsulated inside fatty acid vesicles (Hargreaves and Deamer, 1978; Bachman et al., 1992;Walde et al., 1994). The claim is that such structures would display minimal life-like behavior (reproductive and potentially evolutive) if the intravesicle ribozymes catalyze their own replication and the production of membrane molecules at the expenses of certain precursors available in the environment. The whole process would lead to a spontaneous growth-division of protocells in an allegedly primitive Earth scenario.Leaving aside, for the moment, the mechanistic details and their plausibility, the fundamental and explicit message of that paper goes beyond the apparently narrow focus on the origin of life. To a closer inspection, in fact, the Authors put forward an operational methodology for the construction of chemical reacting systems that would show the difficult-to-define property of being alive just by fulfilling a specific structural and

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“…There have also been reported liposome‐based structures containing artificially designed molecular systems which aims to introduce information processing circuits not used by natural cells [11,12] . Just as organisms in nature have evolved from unicellular to multicellular, research on multicompartmentalization of artificial cells has received much attention [13,14] . There have been reports on the adhesion of post‐formed liposomes, [15,16] multicompartment emulsions containing drugs by centrifugal sedimentation, [17] 3D‐printing injection molding of water‐in‐oil emulsion droplets, [18] and re‐exposure of the structure to water to form lipid bilayers [19] .…”

Section: Introductionmentioning

confidence: 99%

“…[11,12] Just as organisms in nature have evolved from unicellular to multicellular, research on multicompartmentalization of artificial cells has received much attention. [13,14] There have been reports on the adhesion of postformed liposomes, [15,16] multicompartment emulsions containing drugs by centrifugal sedimentation, [17] 3D-printing injection molding of water-in-oil emulsion droplets, [18] and re-exposure of the structure to water to form lipid bilayers. [19] These methods typically require sophisticated machinery such as specialized microfluidic channels, modified 3D printers, etc.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous and Driven Growth of Multicellular Lipid Compartments to Millimeter Size from Porous Polymer Structures**

et al. 2022

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This report describes a method to obtain multicellular shaped compartments made by lipids growing from a sponge-like porous structure. Each compartment is several tens of micrometers in diameter and separated by membranes comprised of phospholipid and amphipathic molecules. The multi-compartment structure spontaneously grew to a millimeter scale, driven by an ionic concentration difference between the interior and exterior environments of the sponge. These compartments can also easily incorporate hydrophilic species as a well as smaller materials such as liposomes. Additionally, we showed that mechanical squeezing of the sponge was also effective in producing multicellular bodies. These simple methods to obtain large-scale multicellular compartment of lipid membrane will help future designs and trials of chemical communications on artificial cells.

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The Rise of the Nested Multicompartment Model in Synthetic Cell Research

Cited by 17 publications

References 47 publications

pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells

pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells

A four-track perspective for bottom-up synthetic cells

Spontaneous and Driven Growth of Multicellular Lipid Compartments to Millimeter Size from Porous Polymer Structures**

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