Synthetic cell demonstrations: Difference between revisions

From SynCell
Jump to navigation Jump to search
(Created page with "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 functi...")
 
No edit summary
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.''
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.
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.


Line 5: Line 7:
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.
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.


=== Two-Cell Communication System (Adamala and Boyden, 2016) ===
=== Two-Cell Communication System (Adamala and Boyden, 2017) ===


A pivotal demonstration in synthetic cell research is the 2016 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.
A pivotal demonstration 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-Free Expression Systems in Vesicle Bioreactors (Noireaux Group) ===
=== Cell-Free Expression Systems in Vesicle Bioreactors (Noireaux Group) ===

Revision as of 16:53, 28 August 2025

This page was generated using the 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.

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

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.

Two-Cell Communication System (Adamala and Boyden, 2017)

A pivotal demonstration 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 [1]. 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 [2], [3]. 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-Free Expression Systems in Vesicle Bioreactors (Noireaux Group)

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 [1], [4]. 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 [5], [6]. 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 [7], [8]. 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 [9].

Liposome Fusion and Mechanosensing (Liu Group)

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 [4], [6]. 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 [10], [7]. 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 [6].

Membrane Engineering and Quorum Sensing (Devaraj Group)

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 [6], [7]. 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 [8], [11]. 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 [12], [5]. 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 [13].

Vesicle-Based Artificial Cells and Tissue Engineering (Elani Group)

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 [4], [5]. 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 [10], [5]. 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 [14]. 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 [8], [15]. 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 [6], [16]. 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 [17]. 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 [18]. Examples include synthetic cells producing quorum sensing molecules that can be perceived by natural bacterial populations, demonstrating chemical communication between artificial and living systems [19]. 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

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.

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 [10], [17]. 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 [17], [5]. The group developed complex synthetic cells assembled through pico-injection into droplet-stabilized giant unilamellar vesicles and demonstrated light-activated communication in synthetic tissues [12]. 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 [20].

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 [21]. Examples include coacervate protocells capable of predatory behavior, where enzymatically active coacervates can degrade the membranes of proteinosomes, demonstrating complex intercellular interactions [22]. 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 [23]. 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 [12].

Polymersome-Based Systems

Polymersomes, formed from amphiphilic block copolymers, provide an alternative membrane system that offers enhanced mechanical stability compared to lipid vesicles [10]. 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 [24]. The robust nature of polymersomes makes them suitable for applications in harsh environments while still maintaining the compartmentalization necessary for synthetic cell functions.

Emulsion-Based Multi-Compartmentalized Systems

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 [25]. 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.

Hydrogel-Based Synthetic Cells

Hydrogel particles represent a unique approach to synthetic cell construction, offering three-dimensional matrices that can encapsulate biomolecules while providing mechanical support [10]. 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.

References

  1. ↑ 1.0 1.1 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 4.0 4.1 4.2 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
  5. ↑ 5.0 5.1 5.2 5.3 5.4 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
  6. ↑ 6.0 6.1 6.2 6.3 6.4 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
  7. ↑ 7.0 7.1 7.2 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
  8. ↑ 8.0 8.1 8.2 Is Research on "Synthetic Cells" Moving to the Next Level?. Pasquale Stano. Life (2018). https://doi.org/10.3390/life9010003
  9. ↑ 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
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Interfacing Living and Synthetic Cells as an Emerging Frontier in Synthetic Biology. Yuval Elani. Angewandte Chemie (2021). https://doi.org/10.1002/ange.202006941
  11. ↑ 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
  12. ↑ 12.0 12.1 12.2 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
  13. ↑ Expression of Fatty Acyl-CoA Ligase Drives One-Pot De Novo 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
  14. ↑ 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
  15. ↑ 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
  16. ↑ 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
  17. ↑ 17.0 17.1 17.2 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
  18. ↑ 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
  19. ↑ 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
  20. ↑ 3D-printed synthetic tissues. Michael J. Booth, Hagan Bayley. The Biochemist (2016). https://doi.org/10.1042/bio03804016
  21. ↑ 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
  22. ↑ 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
  23. ↑ From protocells to prototissues: a materials chemistry approach. Pierangelo Gobbo. Biochemical Society Transactions (2020). https://doi.org/10.1042/bst20200310
  24. ↑ 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
  25. ↑ 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
Retrieved from "https://syncellwiki.org/wiki/index.php?title=Synthetic_cell_demonstrations&oldid=516"