Indeed, animal and plant anatomies are a testament to the level of complexity and specialization achievable by nature. For the purpose of understanding how synthetic biology can assist in producing engineered materials, it is important to consider how biological materials can be made, and how bioengineers have often approached this problem.
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For example, metabolic engineers have often tackled the problem of converting simple sugars and cellulosic biomass into useful substances. Over the past few decades [ 53 ], they have developed the catalytic capacity of organisms in the conversion of five-ring and six-ring carbon sources into useful organic molecules like drugs [ 54 ] and fuels [ 55 ]. By mapping the metabolic pathways of microbial organisms, they have been able to predictively model and experimentally confirm the conversion of these metabolites by cascades of intracellular reactions [ 56 , 57 ].
Several of the key components now useful in synthetic biology are a direct result of these approaches and were specifically developed to control these processes [ 58 — 61 ]. While the line between these disciplines is blurry [ 62 , 63 ], synthetic biology is certainly characterized by a drive toward the development of more complex pathways, cellular components and design-and-build approaches.
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In the case of materials synthesis, potential challenges loom in the production of complicated materials [ 64 , 65 ] and patterns [ 66 — 68 ]. Biological patterning is critical in the material scaffold systems widely used in biomaterial design and synthesis. Just as the engineered protein scaffolds described above enabled the development of intracellular signaling circuits in yeast [ 11 ], patterned material scaffolds can coordinate extracellular binding events as well, and thus, extracellular material assembly.
This paradigm has impacted broad fields ranging from tissue engineering [ 69 ] to molecular self-assembly for nanoelectronics e. As a result, strategies incorporating synthetic biology into biological patterning could be critical in leveraging cellular processes to build materials. A robust example of biological patterning was reported by the Weiss group in work that coupled components of bacterial quorum sensing with engineered pigment changes.
Some bacteria can naturally alter their behavior based upon their cellular density around them in a process known as quorum sensing [ 74 , 75 ]. In these bacterial species, individual cells have the ability to secrete quorum sensing molecules. The bacteria then detect elevated levels of these secreted molecules and alter their behavior. Using this process, bacteria can regulate a range behaviors including bioluminescence [ 76 ], biosurfactant synthesis [ 77 ] and extracellular polymer production [ 78 — 80 ].
In another interesting study, the Voigt lab expanded upon their work with light-detection to develop a synthetic circuit that allowed a lawn of bacteria to distinguish the edges of projected silhouettes [ 68 ]. These first circuits, driving synthetic biological pattern formation, portend increasingly complicated engineered biological patterns.
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To this end, we can look at embryogenesis, the process by which a single fertilized egg grows into uniquely patterned tissues. In a now widely accepted model, Turing proposed that interactions between two molecular morphogens could give rise to the complicated patterns seen in development [ 81 ].
These reaction networks are especially amenable to synthetic biology, and synthetic biological circuits that alter these networks could potentially control the patterning of molecular scaffolds through engineered cellular secretion machinery [ 82 ]. Pattern formation resulting from morphogens: a passively diffusing morphogens result in simple gradients capable yielding basic striped patterns and b interacting morphogens result in oscillations capable of yielding more complicated patterns [ 66 ].
In addition to engineering biological systems to secrete patterned scaffolds for molecular assembly, control of biological systems producing more complex molecular assemblies is also possible. Although it has been widely understood that eukaryotic cells contain compartmental organelles, several important examples of primitive organelles have now been observed in bacteria as well. These microcompartments and nanocompartments can form either as a result of protein shells that allow the internal assembly of materials [ 84 ], or through complex processes that coordinate the assembly of internal material structures [ 83 ].
For example, in structures called carboxysomes [ 14 ], bacteria can synthesize protein shells that resemble virus capsids and contain carbon.
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These nanoscale inclusions have now been widely studied, and reengineered compartments can have been transferred between heterologous hosts [ 85 ]. These approaches may yield new intracellular nanoscale particles, as well as compartments housing cascades of designed reactions for the production of critical biomolecules [ 86 ], thus following an intracellular nanofactory paradigm [ 3 ].
Beyond compartments formed by protein shells, some bacteria have the capacity to form even more complicated internal compartments. As an example, magnetotactic bacteria MTB synthesize linear chains of ferromagnetic particles that effectively serve as compass needles [ 87 ], allowing them to orient their movements with the geomagnetic field [ 15 ].
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These crystals are spatially coordinated within the cell by structural scaffold proteins. In one example, when a scaffold gene was removed, crystals still formed but would no longer spatially arrange in a linear fashion [ 89 ]. Thus, synthetic circuits that control the expression of these key genes could potentially shape the assembly of these nanoparticles and their intracellular superstructure. Hypothesized mechanism of magnetosomes in MTB. Two efforts to synthetically engineer magnetic nanoparticles in living cells were recently published in separate studies by the groups of Martin Fussenegger and Pamela Silver, showing the production of magnetic nanoparticles within mammalian [ 90 ] and yeast cells [ 91 ], respectively.
While insufficient for ferromagnetic behavior, these particles produced paramagnetic behavior that was sufficient to allow cells to be separated from non-magnetic cells in complex cell mixtures. Superparamagnetic nanoparticles programmed by a synthetic network and synthesized in HEK cells [ 90 ]. Synthetic biology has tremendous potential in creating cells that produce biological nanomaterials. Engineered biological circuits and control structures continue to improve, along with the computational and software tools necessary to optimize design with synthetic components.
Concurrently, synthetic biologists are tackling problems in the development of new patterning approaches and the development of new microscale and nanoscale intracellular compartments. As these technologies evolve toward creating nanoscale biomaterials, it will be critical to integrate new synthetic patterning and materials synthesis components into collections of synthetic biology parts and tools.
Ultimately, synthetic biology holds the potential to transform engineered biological cells beyond their role as metabolic catalysts in the production of simple organic molecules, allowing cells to serve as cellular foundries and nanofactories. National Center for Biotechnology Information , U. Sci Technol Adv Mater. Published online Dec 3. Author information Article notes Copyright and License information Disclaimer. Email: ude. Any further distribution of this work must maintain attribution to the author s and the title of the work, journal citation and DOI.
This article has been cited by other articles in PMC. Abstract Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. Keywords: Synthetic biology, Biomaterials, Gene circuits, Cellular engineering. Introduction: synthetic biology and its potential in materials science Synthetic biology is revolutionizing approaches to cellular engineering and has already shown the potential to impact cell-based materials science.
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Synthetic biology's potential in materials science and nanoengineering Nanobiomaterials are synthesized across the different biological species ranging from bacteria to animals. Open in a separate window. Figure 1. Engineering synthetic circuits Synthetic gene circuits For the first synthetic circuits to be engineered, several molecular biological control components were required, all of which are ultimately encoded in the cell's DNA.
Figure 2. Synthetic biology using proteins: components and circuits As discussed above, engineering circuits that rely on DNA—protein interactions has been one major thrust in synthetic biology; yet, another key thrust has been the development of protein—protein signaling components.
Figure 4. Figure 5. Synthetic biology: rapid prototyping Several key challenges must be overcome to build and expand upon the systems described above. Figure 6. Biological material production Engineering materials synthesis In order to deploy synthetic biology in natural biological materials synthesis pathways, it is critical to understand how natural systems produce biomaterials. Natural and synthetic biological pattern formation Biological patterning is critical in the material scaffold systems widely used in biomaterial design and synthesis.
Figure 7. Nanomaterial assembly in biological compartments In addition to engineering biological systems to secrete patterned scaffolds for molecular assembly, control of biological systems producing more complex molecular assemblies is also possible. Figure 8. Figure 9. Conclusions and outlook Synthetic biology has tremendous potential in creating cells that produce biological nanomaterials. Biomimetism and bioinspiration as tools for the design of innovative materials and systems Nature Mater. Artificial cells: building bioinspired systems using small-scale biology Trends Biotechnol.
Towards an in vivo biologically inspired nanofactory Nature Nanotechnol. Environmental signal integration by a modular AND gate. Diversity-based, model-guided construction of synthetic gene networks with predicted functions Nature Biotechnol. Developer's and user's guide to Clotho v2. Eugene—a domain specific language for specifying and constraining synthetic biological parts, devices, and systems. Molecular mechanisms of compartmentalization and biomineralization in magnetotactic bacteria FEMS Microbiol. The role of the magnetite-based receptors in the beak in pigeon homing Curr.
In vivo synthesis of diverse metal nanoparticles by recombinant Escherichia coli Angew. Edn Engl. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter J. A theory for controlling cell cycle dynamics using a reversibly binding inhibitor Proc. Natl Acad. Rewritable digital data storage in live cells via engineered control of recombination directionality Proc. Synthetic circuits integrating logic and memory in living cells Nature Biotechnol. Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator.