Expanding the Toolkit of Synthetic Biology with Biophysics

Synthetic biology has come a long way since its birth at the turn of the millennium. In the early days, it was confined to small-scale tinkering with metabolic pathways and single-gene expression constructs. But as the field has grown and matured, so too has its ambition. Today, synthetic biologists are building complex gene circuits, programming cells to perform novel functions, and exploring the frontiers of biological design.

At the heart of this progress is biophysics. Biophysics is the study of the physical principles that govern biological systems, such as the forces that hold proteins together, or the mechanical properties of cell membranes. By leveraging these principles, synthetic biologists are able to create more sophisticated and robust synthetic systems.

One area where biophysics has had a particularly big impact is in the construction of artificial gene networks. Gene networks are the circuits of genetic information that control the behavior of cells, such as the switch that turns on insulin production in response to high blood sugar. Synthetic biologists have been working to develop new kinds of gene networks that can perform more complex tasks, such as logic operations or temporal patterning. These networks rely on the precise control of gene expression, which is where biophysics comes in.

For example, one recent breakthrough in synthetic gene circuitry is the use of RNA aptamers. Aptamers are short RNA molecules that can bind to specific target molecules, like a lock and key. Synthetic biologists have engineered RNA aptamers that can recognize a wide variety of molecules, from small chemicals to proteins to whole cells. By incorporating these aptamers into gene networks, researchers can make cells respond to specific signals, like the presence of a particular drug or the proximity of another cell.

But designing these networks is a challenge. Gene expression is a complex process that involves a myriad of internal and external factors, from promoter strength to cellular context to environmental conditions. To create reliable gene circuits, synthetic biologists need to account for all these variables. This is where biophysics comes in.

Biophysical models can help predict how gene expression will behave under different conditions. For example, one recent study used a biophysical model to predict the behavior of a temporal gene network that oscillates between two gene expression states. The model accurately predicted the responses of the network to different environmental conditions, and even identified new design strategies that can improve its robustness.

Biophysics is also essential for understanding the physical properties of biological materials, such as the mechanical forces that shape cells. Researchers are using biophysics to design new kinds of biomaterials that can be used for drug delivery, tissue engineering, and even energy production.

For example, one recent advance is the development of self-assembling protein nanocages. These cages are made up of repeating protein subunits that spontaneously assemble into a three-dimensional structure. Researchers have engineered these cages to bind to specific drugs, and have shown that they can be used to target cancer cells in vitro. The strength and rigidity of the cages is determined by their biophysical properties, such as the electrostatic interactions between the subunits.

Another exciting area of research is synthetic photosynthesis. Photosynthesis is the process by which plants convert sunlight into energy, and synthetic biologists are now trying to create artificial photosynthesis systems that can generate clean energy from sunlight. To do this, they need to understand the biophysical principles that govern light absorption, electron transfer, and energy conversion.

One promising approach is to use engineered bacteria that can harness the power of photosynthesis to produce hydrogen gas. These bacteria use specialized proteins called photosynthetic reaction centers to capture light energy, which is then used to split water into hydrogen and oxygen. By using biophysics to optimize the design of these reaction centers, researchers hope to create highly efficient and sustainable energy sources.

Overall, biophysics is an essential tool for synthetic biology. By understanding the physical principles that govern biological systems, synthetic biologists can create more sophisticated and reliable synthetic systems. From gene circuits to biomaterials to photosynthesis, biophysics is expanding the toolkit of synthetic biology like never before. As the field continues to grow and evolve, we can expect even more exciting advances in the years to come.