The fabrication of nano- and microrobots, with “fingers” small enough to “feel” and purposefully manipulate matter at the microscopic scale, is arguably one of the most ambitious goals of nanotechnology. At first glance, the prospect may appear unachievable, with Sci-Fi TV writers – using non-descript “nanobots” as a plot device to achieve any magic that fits the story – certainly carrying some blame in solidifying the notion that they are forever doomed to be a part of the far future.
But the reality is that microrobots are everywhere. Our own bodies produce and destroy billions of them every day: our cells, complex machines carefully programmed through billions of years of evolution to carry out all the functions we need to stay alive. It thus stands to reason that scientists are trying to emulate nature and use its tools in their pursuit of creating synthetic versions of cells.
In this vein, the work that I am doing in the DiMichele lab involves constructing cell-inspired constructs that are made up of DNA. Using nucleic acids for anything else but to carry genetic information might seem strange, but this too can be found in nature. Short bits of RNA called miRNA (microRNA) are found in animals, plants and some viruses, and their purpose is not to encode information but to bind and neutralize other bits of genetic material, thus being able to control the expression of genes.
Nucleic acid nanotechnology is an area of research that takes this concept a step further and uses DNA and RNA also as structural materials. For example, for my work, I am working with condensates (round blobs with controllable dimensions on the order of a few tens of micrometres, fig. 1) that are made up of DNA nanostars (fig. 2) modified with a cholesterol molecule at the ends. The 8 strands that make up the DNA nanostars are rationally designed (i.e. their nucleic base pair sequence is carefully selected) such that they self-assemble into the desired cross shape when added into solution. Using this system, my group has shown that the condensates can be compartmentalized in subsections with different properties (a hallmark property of biological cells), expand and contract in a controlled fashion, and exhibit tunable morphology based on synthesis parameters.
My midi project and subsequent PhD aim to add to this set of functionalities, by engineering the condensates to exhibit controlled growth and self-replication, another key ability of biological cells. This is planned to be achieved through the use of DNA-RNA hybrid condensates, whereby a DNA core carries the “genetic information” of the condensate, which encodes RNA strands which bind with one another to create a pure RNA phase around the core. By adding certain fuels (similar to how bacteria for example require sugar, oxygen and specific biophysical conditions to proliferate), the condensates would grow, bud off, and divide, ensuring that both the genetic material and the structural components are carried over to the offspring. This would bring this system a step closer to a synthetic analogue of the biological cell, the most complex microrobot to date.
NanoDTC PhD Student, c2022