Researchers from the Tokyo Institute of Technology have developed a method to precisely control the timing of division in synthetic DNA droplets, paving the way for more advanced artificial cells and molecular robots.
Mimicking Nature’s Brilliance
Several magnificent features of our body are operated by small and structured less kind of droplets which are referred to as liquid-liquid phase separation (LLPS) droplets. They are also highly versatile, using soft biological materials rather than hard steel or silicon; let them move, change their structure, divide, and reorganize their contents in response to the cell’s requirements.
These have inspired scientists to develop synthetic LLPS droplets that act as analogs of their biological counterparts. Although great strides have been made towards regulating the assembly and flow of these synthetic droplets, coordinating exact time points for these processes has been a big challenge — which has now been addressed.
Time-Division Multiplexing is For the First Time a Reality
An innovative way for manipulating the division timing of synthetic DNA droplets enables unprecedented control in its final foam output, basically turning the droplets into programmable organisms that could lead to an advanced new form of materials discovery research with increased speed and higher resolution than traditional techniques. The researchers also mitigated this issue by constructing a time-delay circuit that controls droplet splitting using inhibitor RNAs and an enzyme called ribonuclease H (RNase H).
The secret to their approach is the Y-shaped DNA nanostructures that are connected using six-branched DNA linkers, binding together the DNA droplets. Such linkers can be cleaved by particular DNA sequences, serving as division triggers. The division triggers initially do bind to proprietary, short fragments of single-stranded RNA (ssRNA) called RNA inhibitors. The RNase H enzyme inactivates these inhibitors by degrading them, enabling a pair of division triggers to cleave DNA linkers and trigger droplet division.
“By this way, the two reactions create a delay in DNA linker cleavage and therefore allow for DNA droplet division at proper timing,” explains Prof. Masahiro Takinoue, senior author of the paper.
Conclusion
This capability to tune the onset of synthetic multi-cell division can open new modes of communication and cooperation for artificial cells and molecular robots. Control of division in this way means that scientists can design more complex and adaptive systems for uses as diverse as drug delivery and diagnostic tools. Although the chemical reactions implemented here are transient, this research lays down a blueprint for practical progress towards the realization of stable non-equilibrium systems that are sustainable and resemble biological processes. The advent of synthetic biology allows for a certain level of control over the regulation of cellular functions concerning time, which will be necessary if artificial cells and molecular machines are ever going to function on a broader scale.
