Designing cells that follow the leader
“Imagine a tiger that is looking for food,” explained Choi. “It senses a chemical trail through smell, and then moves itself to get closer to the food. Those same mechanisms are at work with microorganisms on a molecular scale.”
This kind of nanoscale chemotaxis has been observed in nature, but never replicated in a lab. Choi’s team has constructed a synthetic replica of a biological cell which can be “programmed” to follow the chemical trail left behind by another cell. His research was recently published in the journal Nano Letters.
“Biological systems like cells are complex and intertwined,” said Choi, “so to understand the fundamental mechanisms behind them, we simplify and only study one or two basic mechanisms. In this project, we are studying cell motility and chemotaxis.”
Choi’s team began by designing and creating a synthetic lipid vesicle with DNA components -- a primitive protocell capable of basic movement. By fueling the cell with a certain nucleotide, the cell moves autonomously, and leaves behind a chemical signature. A second cell (the “follow” vesicle) picks up on this chemical trail, and follows the same path as the “lead” vesicle. They were able to observe the movements of these cells using super-resolution microscopy, a powerful technique to observe very small molecular features.
While this project uses synthetic cells as a precedent, Choi is quick to point out that the potential uses are not restricted to biology. “Cells are machines,” said Choi, “and as engineers, our job is to research how their nanomechanical systems work. We have been able to reproduce the mechanics of how they move, and now we have reproduced one of their control systems, using chemotaxis. This has an impact on the fields of engineering, optics, physics, and chemistry, as well as biology.”
More importantly, they are aiming to progress beyond just two species of cells (“lead” and “follow”) to more complex swarming behavior with many different types of cells. “My passion is to develop a strong, diverse, powerful toolbox, using DNA as molecular tools,” said Choi. “By using this programmability we’ve discovered, we can develop mechanical components on a very small scale. We can use these in biomedicine to deliver drugs, or in nanorobotics to manipulate cells. We can program them to measure the tiniest physical characteristics, or act as chemical sensors. That’s the Holy Grail for me.”
Writer: Jared Pike, firstname.lastname@example.org, 765-496-0374
Source: Jong Hyun Choi, email@example.com, 765-496-3562
Mimicking Chemotactic Cell Migration with DNA Programmable Synthetic Vesicles
Jing Pan, Yancheng Du, Hengming Qiu, Luke R. Upton, Feiran Li, and Jong Hyun Choi
Chemotactic cell motility plays a critical role in many biological functions, such as immune response and embryogenesis. Constructing synthetic cell-mimicking systems, such as a dynamic protocell, likewise requires molecular mechanisms that respond to environmental stimuli and execute programmed motility behaviors. Although various molecular components were proposed to achieve diverse functions in synthetic protocells, chemotactic motility on surfaces has not been reported thus far. Here we show directional motility in synthetic lipid vesicles capable of chasing each other by programming DNA components. We demonstrate that the “follow” vesicle recognizes and migrates along the moving trajectory of the “lead” vesicle with an enhanced speed, thus mimicking natural chemotaxis in cell migration. This work provides new possibilities for building synthetic protocells with complex functions such as programmed morphogenesis and cooperative motion. With the vast library of dynamic DNA components, we envision that this platform will enable new discoveries in fundamental sciences and novel applications in biotechnology.