Synthetic cell demonstrations: Difference between revisions

From SynCell
Jump to navigation Jump to search
 
(39 intermediate revisions by the same user not shown)
Line 1: Line 1:
''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 behaviors that can be incorporated into more complex synthetic cell-based systems.


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 ==
This section describes selected examples of synthetic cell-based systems where the compartment is a lipid bilayer vesicle.


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.
=== Engineering Genetic Circuit Interactions Within and Between Synthetic Minimal Cells (2017) ===
[[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.]]


=== Two-Cell Communication System (Adamala et al., 2017) ===
Adamala and Boyden demonstrated the first robust example of genetic circuit-based communication between populations of synthetic cells. 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.


[[Image:adamala_syncell.jpg|400px|thumb|alt={Adamala et al., 2017 Figure 1}|
Adamala, K. P., Martin-Alarcon, D. A., Guthrie-Honea, K. R., & Boyden, E. S. (2017). [https://doi.org/10.1038/nchem.2644 Engineering genetic circuit interactions within and between synthetic minimal cells]. Nature Chemistry, 9(5), 431-439.
Overview of genetic circuit interactions within and between synthetic cells. Adamala et al, 2017<ref name="Adamala2017"/>.]]
<br style="clear: both;" />


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.
=== Cell-Sized Mechanosensitive and Biosensing Compartment Programmed with DNA (2017) ===


=== Cell-Free Expression Systems in Vesicle Bioreactors (Noireaux Group) ===
[[Image:liu-2017.png|300px|thumb|alt={Booth et al., 2016, Figure 2}|
Mechanosensitive and biosensing synthetic cell system. Majumder et al., 2017, Figure 4.]]


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>.
Liu's group at the University of Michigan, in collaboration with Vincent Noireaux at the University of Minnesota, demonstrated synthetic cells capable of coupling mechanical input to biosensing through genetically programmed components. The system used liposomes containing cell-free transcription-translation (TX-TL) reactions that expressed two key proteins: the E. coli mechanosensitive channel of large conductance (MscL) and the calcium biosensor G-GECO. They showed that osmotic pressure changes could activate MscL channels in the synthetic cell membrane, allowing calcium influx that was detected by the co-expressed G-GECO protein through a 23-26 fold increase in fluorescence.


=== Liposome Fusion and Mechanosensing (Liu Group) ===
Majumder, S., Garamella, J., Wang, Y. L., DeNies, M., Noireaux, V., & Liu, A. P. (2017). [https://doi.org/10.1039/C7CC03455E Cell-sized mechanosensitive and biosensing compartment programmed with DNA]. Chemical Communications, 53(53), 7349-7352.
<br style="clear: both;" />


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) ===
[[Image:Kamat-2019.jpg|thumb|300px|Schematic of a membrane AND gate. Hilburger et al., 2019, Figure 1.]]


=== Membrane Engineering and Quorum Sensing (Devaraj Group) ===
Kamat's group at Northwestern developed artificial cells capable of controlled secretion using a membrane-based AND gate that implements Boolean logic through membrane composition changes. The system used giant unilamellar vesicles containing α-hemolysin protein and required both oleic acid (fatty acid) AND the pore-forming protein to achieve cargo release. The key innovation was controlling when α-hemolysin could functionally assemble into membrane pores based on membrane lipid composition. Initially, vesicles with low oleic acid content prevented α-hemolysin from assembling into functional pores, keeping the membrane impermeable. However, when oleic acid micelles were added externally, they incorporated into the vesicle membrane, changing its composition to enable α-hemolysin assembly into functional heptameric channels. This membrane transformation triggered the release of encapsulated cargo such as calcein. The system demonstrated that membrane-based Boolean logic could complement genetic circuits and provided a new method for temporal control of vesicle permeability through membrane protein-lipid interactions.


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>.
Hilburger, C. E., Jacobs, M. L., Lewis, K. R., Peruzzi, J. A., & Kamat, N. P. (2019). [https://doi.org/10.1021/acssynbio.8b00435 Controlling secretion in artificial cells with a membrane AND gate]. ACS Synthetic Biology, 8(6), 1224-1230.
<br style="clear: both;" />


=== Vesicle-Based Artificial Cells and Tissue Engineering (Elani Group) ===
=== TXTL-Based Synthetic Cell Systems (2021) ===
[[Image:Noireaux-20121.jpg|thumb|400px|Cell-free expression and synthesis of deGFP in synthetic cells.. Garenne et al., 2021, Figure 4.]]


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.
Noireaux's group developed the all-E. coli TXTL toolbox 3.0 for creating synthetic cell prototypes using cell-free transcription-translation systems. 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.


=== Bottom-Up Reconstitution of Cellular Machinery (Schwille Group) ===
Garenne, D., Thompson, S., Brisson, A., Khakimzhan, A., & Noireaux, V. (2021). [https://doi.org/10.1093/synbio/ysab017 The all-E. coli TXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform]. Synthetic Biology, 6(1), ysab017.
<br style="clear: both;" />


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


=== Gene-Expressing Liposomes for Molecular Communication ===
[[Image:elani-2023.jpg|400px|thumb|alt={Allen et al., 2013, Figure 1}|
Design and function of the hydrogel artificial cells.. Allen et al., 2023 Figure 1.]]


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.
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 engineered synthetic organelles. They demonstrated artificial cells capable of multiple biomimetic behaviors through modular, interchangeable subcompartments. The system included magnetic particles as "motility organelles" that enabled stimulus-induced movement when exposed to magnetic fields, and lipid vesicle organelles containing encapsulated cargo that could be released in response to specific enzymatic biomarkers. For example, vesicles containing β-galactosidase substrate were embedded within the hydrogel matrix, and when the enzyme was present in the environment, it triggered controlled release of the vesicle contents. The artificial cells also demonstrated enzymatic communication with surrounding bioinspired compartments through cascaded biochemical reactions. This work represents a demonstration of hydrogel-based artificial cells with multiple types of synthetic organelles that could replicate complex cellular behaviors including motility, sensing, content release, and intercellular communication within a single synthetic cell chassis.


== Other Compartmentalization Techniques ==
Allen, M. E., Hindley, J. W., O'Toole, N., Cooke, H. S., Contini, C., Law, R. V., ... & Elani, Y. (2023). [https://doi.org/10.1073/pnas.2307772120 Biomimetic behaviours in hydrogel artificial cells through embedded organelles]. Proceedings of the National Academy of Sciences, 120(35), e2307772120.
<br style="clear: both;" />


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.
=== Self-Organized Spatial Targeting of Contractile Actomyosin Rings for Synthetic Cell Division (2024) ===
[[Image:Schwille-actomyosin-2024.png|thumb|400px|Co-reconstitution of actomyosin networks and the MinDE system enables the reorganization and positioning of actomyosin bundles at mid-cell. Reverte-López et al., 2024, Figure 1.]]


=== Droplet Interface Bilayer Systems (Booth Group) ===
Schwille's group at the Max Planck Institute were able to implement synthetic cell division by successfully combining eukaryotic actomyosin contractile machinery with the bacterial MinDE protein positioning system. The most sophisticated demonstration showed giant unilamellar vesicles containing actomyosin rings that were spatiotemporally positioned at the vesicle equator by MinDE pole-to-pole oscillations through a diffusiophoretic transport mechanism. The MinDE system created active transport of the membrane-bound actomyosin structures via frictional forces, accumulating them at mid-cell in an orientation perpendicular to the oscillation axis. The positioned contractile rings then generated sustained furrow-like membrane invaginations, breaking the spherical symmetry and creating two-lobed vesicles while maintaining the spatial organization. This work represented the first successful integration of spatial positioning machinery with contractile elements to achieve controlled membrane constriction at defined locations, addressing one of the key challenges in synthetic cell division.


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>.
Reverte-López, M., Kanwa, N., Qutbuddin, Y., et al. (2024). [https://doi.org/10.1038/s41467-024-54807-9 Self-organized spatial targeting of contractile actomyosin rings for synthetic cell division]. Nature Communications, 15, 10415.
<br style="clear: both;" />


=== Coacervate-Based Protocells ===
=== Magnetic Activation of Spherical Nucleic Acids for Remote Control of Synthetic Cells (2025) ===


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.
[[Image:parkes-2016.png|240px|thumb|alt={Parkes et al., 2025, Figure 5}|
Controlling α-HL expression and cargo release from synthetic cells with an alternating magnetic field.]]
Booth's group at the University of Oxford and University College London developed synthetic cells controlled by clinically tolerable magnetic fields using spherical nucleic acids with magnetic nanoparticle cores. The system used DNA promoter sequences attached to silica-encapsulated iron oxide nanoparticles that could be activated by alternating magnetic fields at 100 kHz—the only clinically approved frequency for magnetic hyperthermia. When exposed to the magnetic field, localized heating from the nanoparticles released T7 promoter sequences that activated cell-free protein synthesis within giant unilamellar vesicles. The most sophisticated demonstrations showed magnetically controlled expression of mNeonGreen fluorescent protein and α-hemolysin pore-forming protein, which enabled on-demand cargo release from synthetic cells. The system maintained tight control with minimal background activity in the absence of magnetic fields through a novel purification method that removed electrostatically bound DNA. Critically, the technology operated through opaque blocking materials that are impenetrable to current activation methods like light or small molecules, demonstrating the potential of deeply tissue-penetrating magnetic fields for controlling synthetic cells as drug delivery devices.


=== Proteinosome Systems ===
Parkes, E., Al Samad, A., Mazzotti, G., Newell, C., Ng, B., Radford, A., & Booth, M. J. (2025). [https://doi.org/10.1038/s41557-025-01909-6 Magnetic activation of spherical nucleic acids enables the remote control of synthetic cells]. Nature Chemistry (published online).
<br style="clear: both;" />


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" />.
== Other compartmentalization techniques ==


=== Polymersome-Based Systems ===
This section describes selected examples of systems where the compartment is something other than a lipid bilayer-based vesicle.


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.
=== Light-Activated Communication in Synthetic Tissues (2016) ===


=== Emulsion-Based Multi-Compartmentalized Systems ===
[[Image:booth-2016.jpg|400px|thumb|alt={Booth et al., 2016, Figure 2}|
Light-activated expression of LA-mVenus in synthetic cells and synthetic tissues. Booth et al., 2016 Figure 2.]]


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.
Booth and colleagues developed one of the earliest demonstrations of communication between droplet-based synthetic cells using light-activated control systems. 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.


=== Hydrogel-Based Synthetic Cells ===
Booth, M. J., Schild, V. R., Graham, A. D., Olof, S. N., & Bayley, H. (2016). [https://doi.org/10.1126/sciadv.1600056 Light-activated communication in synthetic tissues]. Science Advances, 2(4), e1600056.
<br style="clear: both;" />


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.
=== Communication and Quorum Sensing in Artificial Cells (2018) ===
[[Image:Niederholtmeyer-2018.png|thumb|300px|Communication between cell-mimics via a diffusive genetic activator. Niederholtmeyer et al., 2018, Figure 3.]]


== References ==
Devaraj’s group at UC San Diego developed artificial cells capable of chemical communication using quorum-sensing genetic circuits encapsulated inside a porous polymer membrane containing an artificial hydrogel compartment. "Activator" synthetic cells produced T3 RNAP, which diffused through the polymer membrane into "detector" synthetic cells that expressed GFP. The system demonstrated that non-living vesicle-based mimics could exchange information through diffusible signaling molecules, allowing one population of artificial cells to regulate gene expression in another. This work provided a demonstrations of intercellular communication between synthetic cells and highlighted the potential of quorum sensing as a design principle for coordinating behavior in cell-free systems.
<references />
 
Niederholtmeyer, H., Chaggan, C., & Devaraj, N. K. (2018). [https://doi.org/10.1038/s41467-018-07473-7 Communication and quorum sensing in non-living mimics of eukaryotic cells]. Nature Communications, 9, 5027.
<br style="clear: both;" />
 
=== DNA-Based Communication in Populations of Synthetic Protocells (2019) ===
[[File:Joesaar-2019.png|thumb|400px|PCompartmentalized DNA-based Boolean logic circuits. Joesaar et al, 2019, Figure 5.]]
 
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. 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.
 
Joesaar, A., Yang, S., Bögels, B., van der Linden, A., Pieters, P., Kumar, B. V. V. S. P., ... & de Greef, T. F. A. (2019). [https://doi.org/10.1038/s41565-019-0399-9 DNA-based communication in populations of synthetic protocells]. Nature Nanotechnology, 14(4), 369-378.
<br style="clear: both;" />

Latest revision as of 07:26, 29 September 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 behaviors that can be incorporated into more complex synthetic cell-based systems.

Vesicle-based demonstrations

This section describes selected examples of synthetic cell-based systems where the compartment is a lipid bilayer vesicle.

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.

Adamala and Boyden demonstrated the first robust example of genetic circuit-based communication between populations of synthetic cells. 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.

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.

Cell-Sized Mechanosensitive and Biosensing Compartment Programmed with DNA (2017)

{Booth et al., 2016, Figure 2}
Mechanosensitive and biosensing synthetic cell system. Majumder et al., 2017, Figure 4.

Liu's group at the University of Michigan, in collaboration with Vincent Noireaux at the University of Minnesota, demonstrated synthetic cells capable of coupling mechanical input to biosensing through genetically programmed components. The system used liposomes containing cell-free transcription-translation (TX-TL) reactions that expressed two key proteins: the E. coli mechanosensitive channel of large conductance (MscL) and the calcium biosensor G-GECO. They showed that osmotic pressure changes could activate MscL channels in the synthetic cell membrane, allowing calcium influx that was detected by the co-expressed G-GECO protein through a 23-26 fold increase in fluorescence.

Majumder, S., Garamella, J., Wang, Y. L., DeNies, M., Noireaux, V., & Liu, A. P. (2017). Cell-sized mechanosensitive and biosensing compartment programmed with DNA. Chemical Communications, 53(53), 7349-7352.

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

Schematic of a membrane AND gate. Hilburger et al., 2019, Figure 1.

Kamat's group at Northwestern developed artificial cells capable of controlled secretion using a membrane-based AND gate that implements Boolean logic through membrane composition changes. The system used giant unilamellar vesicles containing α-hemolysin protein and required both oleic acid (fatty acid) AND the pore-forming protein to achieve cargo release. The key innovation was controlling when α-hemolysin could functionally assemble into membrane pores based on membrane lipid composition. Initially, vesicles with low oleic acid content prevented α-hemolysin from assembling into functional pores, keeping the membrane impermeable. However, when oleic acid micelles were added externally, they incorporated into the vesicle membrane, changing its composition to enable α-hemolysin assembly into functional heptameric channels. This membrane transformation triggered the release of encapsulated cargo such as calcein. The system demonstrated that membrane-based Boolean logic could complement genetic circuits and provided a new method for temporal control of vesicle permeability through membrane protein-lipid interactions.

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.

TXTL-Based Synthetic Cell Systems (2021)

Cell-free expression and synthesis of deGFP in synthetic cells.. Garenne et al., 2021, Figure 4.

Noireaux's group developed the all-E. coli TXTL toolbox 3.0 for creating synthetic cell prototypes using cell-free transcription-translation systems. 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.

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.

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

{Allen et al., 2013, Figure 1}
Design and function of the hydrogel artificial cells.. Allen et al., 2023 Figure 1.

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 engineered synthetic organelles. They demonstrated artificial cells capable of multiple biomimetic behaviors through modular, interchangeable subcompartments. The system included magnetic particles as "motility organelles" that enabled stimulus-induced movement when exposed to magnetic fields, and lipid vesicle organelles containing encapsulated cargo that could be released in response to specific enzymatic biomarkers. For example, vesicles containing β-galactosidase substrate were embedded within the hydrogel matrix, and when the enzyme was present in the environment, it triggered controlled release of the vesicle contents. The artificial cells also demonstrated enzymatic communication with surrounding bioinspired compartments through cascaded biochemical reactions. This work represents a demonstration of hydrogel-based artificial cells with multiple types of synthetic organelles that could replicate complex cellular behaviors including motility, sensing, content release, and intercellular communication within a single synthetic cell chassis.

Allen, M. E., Hindley, J. W., O'Toole, N., Cooke, H. S., 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(35), e2307772120.

Self-Organized Spatial Targeting of Contractile Actomyosin Rings for Synthetic Cell Division (2024)

Co-reconstitution of actomyosin networks and the MinDE system enables the reorganization and positioning of actomyosin bundles at mid-cell. Reverte-López et al., 2024, Figure 1.

Schwille's group at the Max Planck Institute were able to implement synthetic cell division by successfully combining eukaryotic actomyosin contractile machinery with the bacterial MinDE protein positioning system. The most sophisticated demonstration showed giant unilamellar vesicles containing actomyosin rings that were spatiotemporally positioned at the vesicle equator by MinDE pole-to-pole oscillations through a diffusiophoretic transport mechanism. The MinDE system created active transport of the membrane-bound actomyosin structures via frictional forces, accumulating them at mid-cell in an orientation perpendicular to the oscillation axis. The positioned contractile rings then generated sustained furrow-like membrane invaginations, breaking the spherical symmetry and creating two-lobed vesicles while maintaining the spatial organization. This work represented the first successful integration of spatial positioning machinery with contractile elements to achieve controlled membrane constriction at defined locations, addressing one of the key challenges in synthetic cell division.

Reverte-López, M., Kanwa, N., Qutbuddin, Y., et al. (2024). Self-organized spatial targeting of contractile actomyosin rings for synthetic cell division. Nature Communications, 15, 10415.

Magnetic Activation of Spherical Nucleic Acids for Remote Control of Synthetic Cells (2025)

{Parkes et al., 2025, Figure 5}
Controlling α-HL expression and cargo release from synthetic cells with an alternating magnetic field.

Booth's group at the University of Oxford and University College London developed synthetic cells controlled by clinically tolerable magnetic fields using spherical nucleic acids with magnetic nanoparticle cores. The system used DNA promoter sequences attached to silica-encapsulated iron oxide nanoparticles that could be activated by alternating magnetic fields at 100 kHz—the only clinically approved frequency for magnetic hyperthermia. When exposed to the magnetic field, localized heating from the nanoparticles released T7 promoter sequences that activated cell-free protein synthesis within giant unilamellar vesicles. The most sophisticated demonstrations showed magnetically controlled expression of mNeonGreen fluorescent protein and α-hemolysin pore-forming protein, which enabled on-demand cargo release from synthetic cells. The system maintained tight control with minimal background activity in the absence of magnetic fields through a novel purification method that removed electrostatically bound DNA. Critically, the technology operated through opaque blocking materials that are impenetrable to current activation methods like light or small molecules, demonstrating the potential of deeply tissue-penetrating magnetic fields for controlling synthetic cells as drug delivery devices.

Parkes, E., Al Samad, A., Mazzotti, G., Newell, C., Ng, B., Radford, A., & Booth, M. J. (2025). Magnetic activation of spherical nucleic acids enables the remote control of synthetic cells. Nature Chemistry (published online).

Other compartmentalization techniques

This section describes selected examples of systems where the compartment is something other than a lipid bilayer-based vesicle.

Light-Activated Communication in Synthetic Tissues (2016)

{Booth et al., 2016, Figure 2}
Light-activated expression of LA-mVenus in synthetic cells and synthetic tissues. Booth et al., 2016 Figure 2.

Booth and colleagues developed one of the earliest demonstrations of communication between droplet-based synthetic cells using light-activated control systems. 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.

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.

Communication and Quorum Sensing in Artificial Cells (2018)

Communication between cell-mimics via a diffusive genetic activator. Niederholtmeyer et al., 2018, Figure 3.

Devaraj’s group at UC San Diego developed artificial cells capable of chemical communication using quorum-sensing genetic circuits encapsulated inside a porous polymer membrane containing an artificial hydrogel compartment. "Activator" synthetic cells produced T3 RNAP, which diffused through the polymer membrane into "detector" synthetic cells that expressed GFP. The system demonstrated that non-living vesicle-based mimics could exchange information through diffusible signaling molecules, allowing one population of artificial cells to regulate gene expression in another. This work provided a demonstrations of intercellular communication between synthetic cells and highlighted the potential of quorum sensing as a design principle for coordinating behavior in cell-free systems.

Niederholtmeyer, H., Chaggan, C., & Devaraj, N. K. (2018). Communication and quorum sensing in non-living mimics of eukaryotic cells. Nature Communications, 9, 5027.

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

PCompartmentalized DNA-based Boolean logic circuits. Joesaar et al, 2019, Figure 5.

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. 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.

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.

Retrieved from "https://syncellwiki.org/wiki/index.php?title=Synthetic_cell_demonstrations&oldid=589"