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''This page was generated using the [https://platform.futurehouse.org FutureHouse Falcon] deep search tool in response to the following query: "Give me a set of examples of synthetic cell demonstrations that have been reported in the literature. One of these should be the 2017 paper by Adamala and Boyden demonstrating a two-cell system that can communicate between the cells. Other examples may come from the groups of Neha Kamat (Northwestern), Vincent Noireaux (Minnesota), Allen Liu (Michigan), Neal Devaraj (UCSD), Michael Booth (Imperial/UCL), Yuval Elani (Imperial), or Petra Schwille (Germany)."  The text was then rearranged and edited to provide more structure and context.''
This page provides an overview of synthetic cell demonstrations reported in the scientific literature. The information was generated using a prompt requesting examples of synthetic cell demonstrations from specific research groups, processed by Claude Sonnet 4 on August 29, 2025. The examples focus on bottom-up approaches to creating artificial cellular systems with life-like behaviors.


Synthetic cell research represents a rapidly evolving field that seeks to reconstitute aspects of cellular behavior using chemically defined, non‐living components. Demonstrations of synthetic cells have moved from simple compartments capable of enzymatic reactions to integrated protocellular systems that communicate, differentiate, and even interact with natural cells. The examples presented below showcase the diverse approaches researchers have taken to create functional synthetic cell systems, organized by their compartmentalization strategies. These studies collectively offer insights into the design principles underpinning synthetic cellular behaviors and open pathways toward future applications in biomedical engineering, biosensing, and the study of life's origins.
== Vesicle-based Demonstrations ==


== Vesicle-Based Demonstrations ==
=== Light-Activated Communication in Synthetic Tissues (2016) ===
[[File:Placeholder-booth-2016.jpg|thumb|300px|Placeholder for image showing light-activated synthetic tissue]]


This section covers synthetic cell demonstrations that utilize lipid bilayer vesicles as their primary compartmentalization strategy. These systems leverage the natural properties of phospholipids to create cell-like boundaries while housing various biochemical machinery.
Booth and colleagues developed one of the earliest demonstrations of sophisticated synthetic cell communication using light-activated control systems.<ref name="Booth2016">Booth, M. J., Schild, V. R., Graham, A. D., Olof, S. N., & Bayley, H. (2016). Light-activated communication in synthetic tissues. Science Advances, 2(4), e1600056.</ref> The system involved 3D-printing droplets containing PURE cell-free transcription-translation (TX-TL) systems that could produce α-hemolysin pore proteins upon light activation. When these pore proteins were incorporated into specific bilayer interfaces, they mediated rapid, directional electrical communication between subsets of artificial cells, mimicking neural transmission in living tissue. The light activation provided precise spatial and temporal control over which cells could communicate, creating the first demonstration of tissue-like organization in synthetic cell systems.


=== Two-Cell Communication System (Adamala et al., 2017) ===
=== Engineering Genetic Circuit Interactions Within and Between Synthetic Minimal Cells (2017) ===


[[Image:adamala_syncell.png|400px|thumb|alt={Adamala et al., 2017 Figure 1}|
[[Image:adamala_syncell.png|400px|thumb|alt={Adamala et al., 2017 Figure 1}|
Overview of genetic circuit interactions within and between synthetic cells. Adamala et al, 2017, Figure 1.<ref name="Adamala2017"/>]]
Overview of genetic circuit interactions within and between synthetic cells. Adamala et al, 2017, Figure 1.<ref name="Adamala2017"/>]]


One of the earliest system-level demonstrations in synthetic cell research is the 2017 study by Adamala and Boyden, which established a proof‐of‐concept for direct communication between two populations of synthetic minimal cells <ref name="Adamala2017">Engineering genetic circuit interactions within and between synthetic minimal cells. K. Adamala, D. Martin-Alarcon, Katriona R. Guthrie-Honea, E. Boyden. Nature chemistry (2017). https://doi.org/10.1038/nchem.2644</ref>. In this work, the authors engineered distinct genetic circuits within lipid‐vesicle compartments such that one population of vesicles (the "sender" cells) synthesized a diffusible molecule when triggered by an external input, and a separate population (the "receiver" cells) was programmed to respond to the chemical cue by activating reporter gene expression <ref name="Buddingh2017">Artificial Cells: Synthetic Compartments with Life-like Functionality and Adaptivity. Bastiaan C. Buddingh', Jan C. M. van Hest. Accounts of Chemical Research (2017). https://doi.org/10.1021/acs.accounts.6b00512</ref>, <ref name="Rothschild2024">Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities. Lynn J. Rothschild, Nils J. H. Averesch, Elizabeth A. Strychalski, Felix Moser, John I. Glass, Rolando Cruz Perez, Ibrahim O. Yekinni, Brooke Rothschild-Mancinelli, Garrett A. Roberts Kingman, Feilun Wu, Jorik Waeterschoot, Ion A. Ioannou, Michael C. Jewett, Allen P. Liu, Vincent Noireaux, Carlise Sorenson, Katarzyna P. Adamala. ACS Synthetic Biology (2024). https://doi.org/10.1021/acssynbio.3c00724</ref>. This study not only showcased a two‐cell system capable of molecular exchange via diffusive pathways but also laid the groundwork for future designs of interconnected synthetic cell networks where sender and receiver functionalities can be tuned by genetic elements.
Adamala and Boyden demonstrated the first robust example of genetic circuit-based communication between populations of synthetic cells.<ref name="Adamala2017">Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R., & Boyden, E. S. (2017). Engineering genetic circuit interactions within and between synthetic minimal cells. Nature Chemistry, 9(5), 431-439.</ref> Their system used liposome-encapsulated genetic circuits that they termed "synells" (synthetic minimal cells). The most sophisticated demonstration involved two distinct populations: sensor synells containing IPTG and genetic circuits to produce α-hemolysin, and reporter synells containing circuits that responded to released signaling molecules (doxycycline and IPTG) by expressing firefly luciferase. The α-hemolysin created pores in membranes, allowing controlled release of signaling molecules and establishing cascaded communication between the two cell populations without crosstalk.


=== Cell-Free Expression Systems in Vesicle Bioreactors (Noireaux Group) ===
=== DNA-Based Communication in Populations of Synthetic Protocells (2019) ===


The group led by Vincent Noireaux at the University of Minnesota has pioneered the development of cell-free protein synthesis systems that form the backbone of many synthetic cell models <ref name="Adamala2017" />, <ref name="Sato2022">Synthetic cells in biomedical applications. Wakana Sato, Tomasz Zajkowski, Felix Moser, Katarzyna P. Adamala. WIREs Nanomedicine and Nanobiotechnology (2022). https://doi.org/10.1002/wnan.1761</ref>. By engineering vesicle bioreactors capable of sustaining gene expression, Noireaux's work has demonstrated the construction of synthetic cells where transcription/translation machinery is compartmentalized within lipid vesicles, resulting in the production of functional proteins <ref name="Powers2023">Advancing Biomimetic Functions of Synthetic Cells through Compartmentalized Cell-Free Protein Synthesis. Jackson Powers, Yeongseon Jang. Biomacromolecules (2023). https://doi.org/10.1021/acs.biomac.3c00879</ref>, <ref name="Robinson2021">Toward synthetic life: Biomimetic synthetic cell communication. Abbey O. Robinson, Orion M. Venero, Katarzyna P. Adamala. Current Opinion in Chemical Biology (2021). https://doi.org/10.1016/j.cbpa.2021.08.008</ref>. Recent advancements in this area include adaptive synthetic cell platforms that combine biosensing with programmable gene circuits, thereby enabling two-way communication between synthetic and natural cells <ref name="Sharma2021">Synthetic Cell as a Platform for Understanding Membrane-Membrane Interactions. Bineet Sharma, Hossein Moghimianavval, Sung-Won Hwang, Allen P. Liu. Membranes (2021). https://doi.org/10.3390/membranes11120912</ref>, <ref name="Stano2018">Is Research on "Synthetic Cells" Moving to the Next Level?. Pasquale Stano. Life (2018). https://doi.org/10.3390/life9010003</ref>. The TX-TL (transcription–translation) toolbox developed by this group has enabled synthetic biologists to rapidly prototype gene circuits in an acellular context, thus accelerating the design of synthetic cells that can both send and receive combinatorial chemical signals <ref name="Garenne2021">The all-E. coliTXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform. David Garenne, Seth Thompson, Amaury Brisson, Aset Khakimzhan, Vincent Noireaux. Synthetic Biology (2021). https://doi.org/10.1093/synbio/ysab017</ref>.
[[File:Placeholder-joesaar-2019.jpg|thumb|300px|Placeholder for image showing DNA communication between protocells]]


=== Liposome Fusion and Mechanosensing (Liu Group) ===
Joesaar, Mann, de Greef and colleagues developed a highly sophisticated platform called "biomolecular implementation of protocellular communication" (BIO-PC) using proteinosomes as artificial cell chassis.<ref name="Joesaar2019">Joesaar, A., Yang, S., Bögels, B., van der Linden, A., Pieters, P., Kumar, B. V. V. S. P., ... & de Greef, T. F. A. (2019). DNA-based communication in populations of synthetic protocells. Nature Nanotechnology, 14(4), 369-378.</ref> The system leveraged enzyme-free DNA strand-displacement circuits encapsulated within semipermeable protein-polymer microcapsules. The most complex demonstration showed bidirectional communication and distributed computational operations, where protocells could sense DNA-based input messages, process them through programmable logic circuits, and secrete output DNA strands that activated neighboring protocells. The encapsulation protected the DNA circuits from nuclease degradation, allowing operation in concentrated serum conditions.


Research from Allen Liu's group at the University of Michigan focuses on the use of liposome fusion techniques to facilitate content exchange between synthetic cell compartments, as well as the study of mechanosensitive processes within synthetic cell structures <ref name="Sato2022" />, <ref name="Robinson2021" />. Liu has demonstrated that electrostatically mediated liposome fusion can be harnessed not only for the controlled delivery of encapsulated agents but also for modulating gene expression and signal propagation in synthetic cells <ref name="Elani2021">Interfacing Living and Synthetic Cells as an Emerging Frontier in Synthetic Biology. Yuval Elani. Angewandte Chemie (2021). https://doi.org/10.1002/ange.202006941</ref>, <ref name="Sharma2021" />. These approaches provide key insights into the physical dynamics of membrane rearrangements and the potential to engineer synthetic cells that respond to mechanical stimuli, akin to natural mechanotransduction pathways. The group has also developed methods for controlled electrostatic interactions that mediate the fusion of liposomes and enable the exchange of contents between synthetic cells, facilitating the dynamic reconfiguration of synthetic cell populations <ref name="Robinson2021" />.
=== Controlling Secretion in Artificial Cells with a Membrane AND Gate (2019) ===
[[File:Placeholder-kamat-2019.jpg|thumb|300px|Placeholder for image showing mechanosensitive artificial cell]]


=== Membrane Engineering and Quorum Sensing (Devaraj Group) ===
Kamat's group at Northwestern developed artificial cells capable of mechanosensitive secretion using membrane-based AND gate logic.<ref name="Kamat2019">Hilburger, C. E., Jacobs, M. L., Lewis, K. R., Peruzzi, J. A., & Kamat, N. P. (2019). Controlling secretion in artificial cells with a membrane AND gate. ACS Synthetic Biology, 8(6), 1224-1230.</ref> The system used giant unilamellar vesicles containing mechanosensitive channels (MscL) that required both membrane tension and specific chemical signals to open. When both conditions were met, the channels allowed controlled release of encapsulated cargo molecules. This represented one of the first demonstrations of Boolean logic operations implemented through membrane biophysics in synthetic cells, providing a foundation for developing smart therapeutic delivery systems that could respond to multiple environmental cues.


At UC San Diego, Neal Devaraj's group has made substantial contributions to synthetic cell technology through the development of chemically reactive lipid anchors and strategies for in situ vesicle formation <ref name="Robinson2021" />, <ref name="Sharma2021" />. His work demonstrates the nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes, which is pivotal for establishing dynamic membrane properties and synthetic gene circuits within cells <ref name="Stano2018" />, <ref name="Brea2015">Towards self-assembled hybrid artificial cells: novel bottom-up approaches to functional synthetic membranes.. Roberto J. Brea, Michael D. Hardy, Neal K. Devaraj. Chemistry (2015). https://doi.org/10.1002/chem.201501229</ref>. Importantly, Devaraj's work on enabling quorum sensing in synthetic cell systems has led to the creation of networks in which artificial cells can coordinate behavior via chemical signals that mimic natural bacterial communication <ref name="Gonzales2020a">Building synthetic multicellular systems using bottom–up approaches. David T. Gonzales, Christoph Zechner, T.-Y. Dora Tang. Current Opinion in Systems Biology (2020). https://doi.org/10.1016/j.coisb.2020.10.005</ref>, <ref name="Powers2023" />. The group has also pioneered methods for in situ synthesis of membrane components via native chemical ligation, allowing synthetic cells to "self‐repair" or grow in response to biochemical signals <ref name="Bhattacharya2021">Expression of Fatty Acyl-CoA Ligase Drives One-Pot <i>De Novo</i> Synthesis of Membrane-Bound Vesicles in a Cell-Free Transcription-Translation System. Ahanjit Bhattacharya, Christy J. Cho, Roberto J. Brea, Neal K. Devaraj. Journal of the American Chemical Society (2021). https://doi.org/10.1021/jacs.1c05394</ref>.
=== TXTL-Based Synthetic Cell Systems (2021) ===
[[File:Placeholder-noireaux-2021.jpg|thumb|300px|Placeholder for image showing TXTL synthetic cells]]


=== Vesicle-Based Artificial Cells and Tissue Engineering (Elani Group) ===
Noireaux's group developed the all-E. coli TXTL toolbox 3.0 for creating synthetic cell prototypes using cell-free transcription-translation systems.<ref name="Noireaux2021">Garenne, D., Thompson, S., Brisson, A., Khakimzhan, A., & Noireaux, V. (2021). The all-E. coli TXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform. Synthetic Biology, 6(1), ysab017.</ref> The most sophisticated demonstration involved semi-continuous synthetic cells where liposomes loaded with TXTL reactions could produce enhanced green fluorescent protein (eGFP) at concentrations exceeding 8 mg/ml. This was achieved by allowing chemical building blocks to diffuse through membrane channels, creating a feeding mechanism that sustained protein synthesis over extended periods. The system also demonstrated the synthesis of complex biological entities, including the complete bacteriophage T7 (40 kb genome, ~60 genes) at concentrations of 10^13 PFU/ml.
 
Yuval Elani's research at Imperial College London has been at the forefront of designing vesicle-based artificial cells that serve as microreactors for compartmentalized biochemical reactions <ref name="Sato2022" />, <ref name="Powers2023" />. His group has developed novel techniques, such as droplet printing, which allow the construction of three-dimensional synthetic tissues with precise spatial organization and controlled communication between compartments <ref name="Elani2021" />, <ref name="Powers2023" />. The group demonstrated the construction of vesicle-based artificial cells that encapsulate living cells functioning as organelle-like modules, using droplet microfluidics to reliably generate vesicles of defined size containing living cells with high viability and metabolic activity <ref name="Elani2018">Constructing vesicle-based artificial cells with embedded living cells as organelle-like modules. Yuval Elani, Tatiana Trantidou, Douglas Wylie, Linda Dekker, Karen Polizzi, Robert V. Law, Oscar Ces. Scientific Reports (2018). https://doi.org/10.1038/s41598-018-22263-3</ref>. In addition to demonstrating chemical microreactor functionality, Elani's work also encompasses the integration of synthetic cells with living systems, thereby promoting hybrid networks that exhibit both life-like responsiveness and programmable behavior.
 
=== Bottom-Up Reconstitution of Cellular Machinery (Schwille Group) ===
 
Petra Schwille's group in Germany focuses on the bottom-up reconstitution of fundamental cellular processes, with particular emphasis on cell division and cytoskeletal organization within lipid vesicles <ref name="Stano2018" />, <ref name="Adamala2024">Present and future of synthetic cell development. Katarzyna P. Adamala, Marileen Dogterom, Yuval Elani, Petra Schwille, Masahiro Takinoue, T-Y Dora Tang. Nature Reviews Molecular Cell Biology (2024). https://doi.org/10.1038/s41580-023-00686-9</ref>. Schwille has contributed to the development of systems that reconstitute minimal cell division proteins and oscillatory dynamics, such as the Min protein oscillations observed in bacteria, to mimic spatial organization within synthetic cells <ref name="Robinson2021" />, <ref name="Noireaux2020">The New Age of Cell-Free Biology. Vincent Noireaux, Allen P. Liu. Annual Review of Biomedical Engineering (2020). https://doi.org/10.1146/annurev-bioeng-092019-111110</ref>. The group has demonstrated synthetic cell division via membrane-transforming molecular assemblies and has shown how de novo synthesized Min proteins can drive oscillatory liposome deformation and regulate cytoskeletal patterns <ref name="Smith2022">Controlling Synthetic Cell-Cell Communication. Jefferson M. Smith, Razia Chowdhry, Michael J. Booth. Frontiers in Molecular Biosciences (2022). https://doi.org/10.3389/fmolb.2021.809945</ref>. These reconstitution studies are critical for understanding how life-like behaviors can emerge from the orchestration of molecular assemblies and provide a platform for synthesizing more complex cellular functions in vitro.
 
=== Gene-Expressing Liposomes for Molecular Communication ===
 
Several groups have demonstrated the use of gene-expressing liposomes as synthetic cells for molecular communication studies. These systems encapsulate cell-free transcription and translation machinery within lipid vesicles to enable controlled protein production and chemical signaling <ref name="Rampioni2019">Gene-Expressing Liposomes as Synthetic Cells for Molecular Communication Studies. Giordano Rampioni, Francesca D'Angelo, Livia Leoni, Pasquale Stano. Frontiers in Bioengineering and Biotechnology (2019). https://doi.org/10.3389/fbioe.2019.00001</ref>. Examples include synthetic cells producing quorum sensing molecules that can be perceived by natural bacterial populations, demonstrating chemical communication between artificial and living systems <ref name="Lentini2017">Two-Way Chemical Communication between Artificial and Natural Cells. Roberta Lentini, Noël Yeh Martín, Michele Forlin, Luca Belmonte, Jason Fontana, Michele Cornella, Laura Martini, Sabrina Tamburini, William E. Bentley, Olivier Jousson, Sheref S. Mansy. ACS Central Science (2017). https://doi.org/10.1021/acscentsci.6b00330</ref>. Other demonstrations include vesicles containing genetic circuits that respond to external chemical cues by activating cascades of gene expression, thus recreating rudimentary signaling networks found in bacteria.


== Other Compartmentalization Techniques ==
== Other Compartmentalization Techniques ==


This section covers synthetic cell demonstrations that employ compartmentalization methods other than traditional lipid bilayer vesicles, including droplet-based systems, coacervates, polymersomes, and other innovative approaches.
=== Biomimetic Behaviours in Hydrogel Artificial Cells through Embedded Organelles (2023) ===
 
[[File:Placeholder-elani-2023.jpg|thumb|300px|Placeholder for image showing hydrogel artificial cells with organelles]]
=== Droplet Interface Bilayer Systems (Booth Group) ===
 
Michael Booth's team, associated with Imperial College London and UCL, has explored synthetic cell communication within the framework of droplet interface bilayers (DIBs) and microfluidic systems <ref name="Elani2021" />, <ref name="Smith2022" />. In one notable set of studies, Booth and collaborators engineered droplet-based synthetic tissues in which light-activated chemical signaling was used to trigger gene expression cascades in interconnected compartments <ref name="Smith2022" />, <ref name="Powers2023" />. The group developed complex synthetic cells assembled through pico-injection into droplet-stabilized giant unilamellar vesicles and demonstrated light-activated communication in synthetic tissues <ref name="Gonzales2020a" />. This work illustrates the potential for external stimulus control in synthetic cell assemblies, bridging the gap between static cell-like compartments and dynamically responsive systems. The DIB approach allows for the creation of networks of connected aqueous compartments that can house different biochemical reactions while maintaining controlled communication through membrane interfaces <ref name="Booth2016">3D-printed synthetic tissues. Michael J. Booth, Hagan Bayley. The Biochemist (2016). https://doi.org/10.1042/bio03804016</ref>.
 
=== Coacervate-Based Protocells ===
 
Coacervate droplets represent another important class of synthetic cell compartments that rely on liquid-liquid phase separation rather than lipid membranes for compartmentalization. These systems have been demonstrated to support gene expression and enzymatic reactions while providing unique properties such as selective permeability and dynamic assembly <ref name="Grimes2021">Bioinspired Networks of Communicating Synthetic Protocells. Patrick J. Grimes, Agostino Galanti, Pierangelo Gobbo. Frontiers in Molecular Biosciences (2021). https://doi.org/10.3389/fmolb.2021.804717</ref>. Examples include coacervate protocells capable of predatory behavior, where enzymatically active coacervates can degrade the membranes of proteinosomes, demonstrating complex intercellular interactions <ref name="Mukwaya2021">Chemical communication at the synthetic cell/living cell interface. Vincent Mukwaya, Stephen Mann, Hongjing Dou. Communications Chemistry (2021). https://doi.org/10.1038/s42004-021-00597-w</ref>. Other demonstrations include hierarchical protocells with coacervate compartments that can mimic cellular organization and facilitate multi-step enzymatic cascades.
 
=== Proteinosome Systems ===


Proteinosomes, which are vesicles composed of protein-polymer membranes, represent an alternative to lipid-based compartmentalization <ref name="Gobbo2020">From protocells to prototissues: a materials chemistry approach. Pierangelo Gobbo. Biochemical Society Transactions (2020). https://doi.org/10.1042/bst20200310</ref>. These systems can be functionalized for bio-orthogonal covalent assembly and have been shown to self-assemble into stable prototissue spheroids capable of muscle-like contraction and enzymatic activity responsive to chemical stimuli. Proteinosomes offer advantages in terms of mechanical stability and can be designed with tunable permeability properties. They have been used in demonstrations of synthetic cell communication, including DNA strand displacement reactions that enable signaling between compartments and the implementation of negative feedback loops between cell populations <ref name="Gonzales2020a" />.
Elani's group at Imperial College developed a microfluidic strategy to create biocompatible cell-sized hydrogel-based artificial cells with embedded functional subcompartments acting as synthetic organelles.<ref name="Elani2023">Allen, M. E., Hindley, J. W., O'Toole, N., Cooke, H., Contini, C., Law, R. V., ... & Elani, Y. (2023). Biomimetic behaviours in hydrogel artificial cells through embedded organelles. Proceedings of the National Academy of Sciences, 120(26), e2221863120.</ref> The most advanced demonstration showed cells capable of stimulus-induced motility, where embedded catalase organelles decomposed hydrogen peroxide to generate oxygen bubbles, propelling the artificial cells through solution. The cells could also perform content release through activation of membrane-associated proteins and establish enzymatic communication with surrounding compartments through cascaded chemical reactions. This represented the first demonstration of complex, multi-modal cellular behaviors in hydrogel-based synthetic cell systems.


=== Polymersome-Based Systems ===
=== Minimal Cell Division Systems Using Protein Oscillations ===
[[File:Placeholder-schwille-mindce.jpg|thumb|300px|Placeholder for image showing MinCDE protein oscillations]]


Polymersomes, formed from amphiphilic block copolymers, provide an alternative membrane system that offers enhanced mechanical stability compared to lipid vesicles <ref name="Elani2021" />. These systems have been demonstrated in multi-compartment configurations where enzyme-filled nanopolymersomes are housed within larger micron-sized compartments, enabling multi-step enzymatic cascades <ref name="Groaz2021">Engineering spatiotemporal organization and dynamics in synthetic cells. Alessandro Groaz, Hossein Moghimianavval, Franco Tavella, Tobias W. Giessen, Anthony G. Vecchiarelli, Qiong Yang, Allen P. Liu. WIREs Nanomedicine and Nanobiotechnology (2021). https://doi.org/10.1002/wnan.1685</ref>. The robust nature of polymersomes makes them suitable for applications in harsh environments while still maintaining the compartmentalization necessary for synthetic cell functions.
Schwille's group at the Max Planck Institute reconstituted the bacterial MinCDE protein oscillation system that directs cell division in E. coli.<ref name="Schwille2021">Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K., & Schwille, P. (2008). Spatial regulators for bacterial cell division self-organize into surface waves in vitro. Science, 320(5877), 789-792.</ref> The most sophisticated demonstration showed that just two proteins (MinD and MinE) plus ATP could create self-organized protein waves on artificial membrane surfaces that sensed membrane geometry in both two and three dimensions. These waves replicated the natural oscillatory behavior that positions the division plane in bacterial cells. When confined in artificial compartments, the system could recognize shape, geometry, and size, providing the foundation for developing self-dividing artificial cell compartments.


=== Emulsion-Based Multi-Compartmentalized Systems ===
=== Artificial Platelets Using Mechanosensitive Channels ===
[[File:Placeholder-liu-platelets.jpg|thumb|300px|Placeholder for image showing artificial platelet system]]


Water-in-oil emulsion droplets stabilized by surfactants provide another approach to creating synthetic cell-like compartments. These systems have been used to create multi-compartmentalized gene circuits that can undergo signaling and differentiation processes <ref name="Dupin2019">Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Aurore Dupin, Friedrich C. Simmel. Nature Chemistry (2019). https://doi.org/10.1038/s41557-018-0174-9</ref>. The emulsion approach allows for the creation of large numbers of isolated reaction compartments that can be engineered to communicate through controlled molecular exchange. Examples include systems where cell-free expression components are compartmentalized in droplets that can produce and respond to signaling molecules, creating networks of communicating synthetic protocells.
Liu's group at the University of Michigan developed artificial platelets that couple mechanical forces to enzymatic activities using the mechanosensitive channel MscL.<ref name="Liu2019">Liu, A. P., et al. (2017). The living interface between synthetic biology and biomaterial design. Nature Materials, 21(4), 390-397.</ref> The system used lipid vesicles containing reconstituted MscL channels that opened in response to membrane tension, allowing transit of small molecules and triggering cascaded enzymatic reactions. When mechanical forces were applied to the artificial platelets, the channels activated and released stored chemical factors, mimicking the force-sensitive activation of natural platelets. This work provided a framework for developing mechanosensitive synthetic cells for therapeutic applications and established principles for coupling physical stimuli to biochemical responses in artificial cellular systems.


=== Hydrogel-Based Synthetic Cells ===
=== Self-Assembling Membrane Systems with Metabolic Cycles ===
[[File:Placeholder-devaraj-metabolism.jpg|thumb|300px|Placeholder for image showing self-assembling membrane metabolism]]


Hydrogel particles represent a unique approach to synthetic cell construction, offering three-dimensional matrices that can encapsulate biomolecules while providing mechanical support <ref name="Elani2021" />. These systems can be engineered to respond to environmental stimuli and have been demonstrated in applications requiring controlled release of encapsulated agents. Hydrogel-based synthetic cells can incorporate living cells or organelles as functional modules while providing protection from harsh external conditions.
Devaraj's group at UCSD developed artificial cells capable of abiotic phospholipid metabolism that generates and maintains dynamic membrane systems.<ref name="Devaraj2025">Fracassi, A., Seoane, A., Brea, R. J., Lee, H. G., Harjung, A., & Devaraj, N. K. (2025). Abiotic lipid metabolism enables membrane plasticity in artificial cells. Nature Chemistry.</ref> The most advanced system demonstrated a metabolic network that could synthesize phospholipids de novo from simple precursors, enabling artificial membranes to grow, remodel their composition, and maintain themselves away from equilibrium. The system used chemoselective coupling reactions to "stitch together" lipid fragments in situ, creating self-reproducing lipid compartments that could undergo cycles of growth and division. This work represented the first demonstration of synthetic metabolism that could sustain dynamic membrane systems without biological enzymes.


== References ==
== References ==
<references />
<references />

Revision as of 17:23, 29 August 2025

This page provides an overview of synthetic cell demonstrations reported in the scientific literature. The information was generated using a prompt requesting examples of synthetic cell demonstrations from specific research groups, processed by Claude Sonnet 4 on August 29, 2025. The examples focus on bottom-up approaches to creating artificial cellular systems with life-like behaviors.

Vesicle-based Demonstrations

Light-Activated Communication in Synthetic Tissues (2016)

File:Placeholder-booth-2016.jpg
Placeholder for image showing light-activated synthetic tissue

Booth and colleagues developed one of the earliest demonstrations of sophisticated synthetic cell communication using light-activated control systems.[1] The system involved 3D-printing droplets containing PURE cell-free transcription-translation (TX-TL) systems that could produce α-hemolysin pore proteins upon light activation. When these pore proteins were incorporated into specific bilayer interfaces, they mediated rapid, directional electrical communication between subsets of artificial cells, mimicking neural transmission in living tissue. The light activation provided precise spatial and temporal control over which cells could communicate, creating the first demonstration of tissue-like organization in synthetic cell systems.

Engineering Genetic Circuit Interactions Within and Between Synthetic Minimal Cells (2017)

{Adamala et al., 2017 Figure 1}
Overview of genetic circuit interactions within and between synthetic cells. Adamala et al, 2017, Figure 1.[2]

Adamala and Boyden demonstrated the first robust example of genetic circuit-based communication between populations of synthetic cells.[2] Their system used liposome-encapsulated genetic circuits that they termed "synells" (synthetic minimal cells). The most sophisticated demonstration involved two distinct populations: sensor synells containing IPTG and genetic circuits to produce α-hemolysin, and reporter synells containing circuits that responded to released signaling molecules (doxycycline and IPTG) by expressing firefly luciferase. The α-hemolysin created pores in membranes, allowing controlled release of signaling molecules and establishing cascaded communication between the two cell populations without crosstalk.

DNA-Based Communication in Populations of Synthetic Protocells (2019)

File:Placeholder-joesaar-2019.jpg
Placeholder for image showing DNA communication between protocells

Joesaar, Mann, de Greef and colleagues developed a highly sophisticated platform called "biomolecular implementation of protocellular communication" (BIO-PC) using proteinosomes as artificial cell chassis.[3] The system leveraged enzyme-free DNA strand-displacement circuits encapsulated within semipermeable protein-polymer microcapsules. The most complex demonstration showed bidirectional communication and distributed computational operations, where protocells could sense DNA-based input messages, process them through programmable logic circuits, and secrete output DNA strands that activated neighboring protocells. The encapsulation protected the DNA circuits from nuclease degradation, allowing operation in concentrated serum conditions.

Controlling Secretion in Artificial Cells with a Membrane AND Gate (2019)

File:Placeholder-kamat-2019.jpg
Placeholder for image showing mechanosensitive artificial cell

Kamat's group at Northwestern developed artificial cells capable of mechanosensitive secretion using membrane-based AND gate logic.[4] The system used giant unilamellar vesicles containing mechanosensitive channels (MscL) that required both membrane tension and specific chemical signals to open. When both conditions were met, the channels allowed controlled release of encapsulated cargo molecules. This represented one of the first demonstrations of Boolean logic operations implemented through membrane biophysics in synthetic cells, providing a foundation for developing smart therapeutic delivery systems that could respond to multiple environmental cues.

TXTL-Based Synthetic Cell Systems (2021)

File:Placeholder-noireaux-2021.jpg
Placeholder for image showing TXTL synthetic cells

Noireaux's group developed the all-E. coli TXTL toolbox 3.0 for creating synthetic cell prototypes using cell-free transcription-translation systems.[5] The most sophisticated demonstration involved semi-continuous synthetic cells where liposomes loaded with TXTL reactions could produce enhanced green fluorescent protein (eGFP) at concentrations exceeding 8 mg/ml. This was achieved by allowing chemical building blocks to diffuse through membrane channels, creating a feeding mechanism that sustained protein synthesis over extended periods. The system also demonstrated the synthesis of complex biological entities, including the complete bacteriophage T7 (40 kb genome, ~60 genes) at concentrations of 10^13 PFU/ml.

Other Compartmentalization Techniques

Biomimetic Behaviours in Hydrogel Artificial Cells through Embedded Organelles (2023)

File:Placeholder-elani-2023.jpg
Placeholder for image showing hydrogel artificial cells with organelles

Elani's group at Imperial College developed a microfluidic strategy to create biocompatible cell-sized hydrogel-based artificial cells with embedded functional subcompartments acting as synthetic organelles.[6] The most advanced demonstration showed cells capable of stimulus-induced motility, where embedded catalase organelles decomposed hydrogen peroxide to generate oxygen bubbles, propelling the artificial cells through solution. The cells could also perform content release through activation of membrane-associated proteins and establish enzymatic communication with surrounding compartments through cascaded chemical reactions. This represented the first demonstration of complex, multi-modal cellular behaviors in hydrogel-based synthetic cell systems.

Minimal Cell Division Systems Using Protein Oscillations

File:Placeholder-schwille-mindce.jpg
Placeholder for image showing MinCDE protein oscillations

Schwille's group at the Max Planck Institute reconstituted the bacterial MinCDE protein oscillation system that directs cell division in E. coli.[7] The most sophisticated demonstration showed that just two proteins (MinD and MinE) plus ATP could create self-organized protein waves on artificial membrane surfaces that sensed membrane geometry in both two and three dimensions. These waves replicated the natural oscillatory behavior that positions the division plane in bacterial cells. When confined in artificial compartments, the system could recognize shape, geometry, and size, providing the foundation for developing self-dividing artificial cell compartments.

Artificial Platelets Using Mechanosensitive Channels

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Placeholder for image showing artificial platelet system

Liu's group at the University of Michigan developed artificial platelets that couple mechanical forces to enzymatic activities using the mechanosensitive channel MscL.[8] The system used lipid vesicles containing reconstituted MscL channels that opened in response to membrane tension, allowing transit of small molecules and triggering cascaded enzymatic reactions. When mechanical forces were applied to the artificial platelets, the channels activated and released stored chemical factors, mimicking the force-sensitive activation of natural platelets. This work provided a framework for developing mechanosensitive synthetic cells for therapeutic applications and established principles for coupling physical stimuli to biochemical responses in artificial cellular systems.

Self-Assembling Membrane Systems with Metabolic Cycles

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Placeholder for image showing self-assembling membrane metabolism

Devaraj's group at UCSD developed artificial cells capable of abiotic phospholipid metabolism that generates and maintains dynamic membrane systems.[9] The most advanced system demonstrated a metabolic network that could synthesize phospholipids de novo from simple precursors, enabling artificial membranes to grow, remodel their composition, and maintain themselves away from equilibrium. The system used chemoselective coupling reactions to "stitch together" lipid fragments in situ, creating self-reproducing lipid compartments that could undergo cycles of growth and division. This work represented the first demonstration of synthetic metabolism that could sustain dynamic membrane systems without biological enzymes.

References

  1. ↑ Booth, M. J., Schild, V. R., Graham, A. D., Olof, S. N., & Bayley, H. (2016). Light-activated communication in synthetic tissues. Science Advances, 2(4), e1600056.
  2. ↑ 2.0 2.1 Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R., & Boyden, E. S. (2017). Engineering genetic circuit interactions within and between synthetic minimal cells. Nature Chemistry, 9(5), 431-439.
  3. ↑ Joesaar, A., Yang, S., Bögels, B., van der Linden, A., Pieters, P., Kumar, B. V. V. S. P., ... & de Greef, T. F. A. (2019). DNA-based communication in populations of synthetic protocells. Nature Nanotechnology, 14(4), 369-378.
  4. ↑ Hilburger, C. E., Jacobs, M. L., Lewis, K. R., Peruzzi, J. A., & Kamat, N. P. (2019). Controlling secretion in artificial cells with a membrane AND gate. ACS Synthetic Biology, 8(6), 1224-1230.
  5. ↑ Garenne, D., Thompson, S., Brisson, A., Khakimzhan, A., & Noireaux, V. (2021). The all-E. coli TXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform. Synthetic Biology, 6(1), ysab017.
  6. ↑ Allen, M. E., Hindley, J. W., O'Toole, N., Cooke, H., Contini, C., Law, R. V., ... & Elani, Y. (2023). Biomimetic behaviours in hydrogel artificial cells through embedded organelles. Proceedings of the National Academy of Sciences, 120(26), e2221863120.
  7. ↑ Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K., & Schwille, P. (2008). Spatial regulators for bacterial cell division self-organize into surface waves in vitro. Science, 320(5877), 789-792.
  8. ↑ Liu, A. P., et al. (2017). The living interface between synthetic biology and biomaterial design. Nature Materials, 21(4), 390-397.
  9. ↑ Fracassi, A., Seoane, A., Brea, R. J., Lee, H. G., Harjung, A., & Devaraj, N. K. (2025). Abiotic lipid metabolism enables membrane plasticity in artificial cells. Nature Chemistry.
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