Using cancer cells as logic gates to determine what moves them – ScienceDaily

Using cancer cells as logic gates to determine what moves them – ScienceDaily

Cancer cells migrate through the body for several reasons; Some simply follow the flow of a liquid, while others actively follow specific chemical trails. So how do you determine which cells are moving and why? Purdue University researchers reverse engineered a cellular signal processing system and used it like a logic gate – a simple computer – to better understand what causes certain cells to migrate.

Mechanical engineering professor Bumsoo Han and his research group have been studying cancer cells for many years. He builds microfluidic structures to simulate their biological environment; He even used these structures to build a “time machine” to reverse the growth of pancreatic cancer cells.

“In our experiments, we observed and studied how these cancer cells migrate because this is an important aspect of cancer metastasis,” said Hye-ran Moon, a postdoctoral researcher in Han’s team. “But this is different. We try to address the basic mechanisms behind these behaviors. And it’s very challenging because cells are very complex systems of molecules and they’re exposed to multiple cues that make them move.”

One of those clues is chemical trails, to which many cells are naturally attracted (much like ants following a scent trail). Another is fluid flow; When liquids flow around cells in a certain direction, many cells will simply go with it. So if a cell is moving, how can you tell if it’s motivated by chemicals, fluid movement, or both?

The team used a ternary logic gate model to analyze these cues and predict how cells would move under different environments. Their research was published in Laboratory on a chipa journal of the Royal Society of Chemistry.

Their experiments took place in a microfluidic platform with a central chamber for the cells and two side platforms. With this device, they could replicate fluid flow in one direction, the opposite direction, or no flow at all. They could also introduce a chemical that is known to cause the cells to migrate. Again, they had the option of chemotaxis in one direction, in the opposite direction, or none at all. Would these two clues multiply or cancel each other out?

“With each two clues and three choices, we had enough observable data to create a ternary logic gate model,” Moon said.

Logic gates are a computing construct in which transistors accept a 1 or 0 input and return a 1 or 0 output. Binary logic gates take a combination of two ones and two zeros and output different results depending on what type of gate it is. Ternary logic gates do the same thing, except with three possible inputs and outputs: 1, 0, and -1.

Moon assigned values ​​to which direction the cells moved under the two different stimuli. “If the cells have moved downstream, that’s 1,” Moon said. “If they have no direction, that’s 0. If they’re moving in the opposite direction to the flow, that’s -1.”

When cells encountered either chemicals individually or a stream of liquid, they moved in the positive direction (the “1”). If both were present in the same direction, the effect was additive (still “1”). However, when the two flowed in opposite directions, the cells moved in the direction of the chemicals (the “-1”) rather than the direction of fluid flow.

Based on these observations, Moon extrapolated a 3×3 grid to simplify the results. The clues from these cancer cells could now graph an electrical circuit much like an electrical engineer would.

Of course, the real world is never that simple. “In fact, the chemical stimulus is a gradient, not an on-off switch,” Moon said. “The cells do not move until a certain threshold of flux has been introduced; and if you insert too much, the cell will short out and not move at all. The accuracy with which we can predict this movement is not linearly related.”

Moon also emphasized that this particular experiment is very simple: two stimuli in strictly opposite directions in a single dimension. The next step would be to build a similar experiment but in a two dimensional plane; and then another in a three-dimensional volume. And thats just the beginning; Once you add multiple stimuli and consider time as the fourth dimension, the calculations become incredibly complex. “Now you understand why biologists need to use supercomputers!” said moon.

This study was conducted in collaboration with the Purdue Institute for Cancer Research; the Weldon School of Biomedical Engineering; the Purdue Department of Physics and Astronomy; and Andrew Mugler and Soutick Saha from the University of Pittsburgh’s Department of Physics and Astronomy.

“This is a perfect example of how microfluidic devices can be used in cancer research,” said Moon. “Performing this experiment in a biological setting would be extremely difficult. But with these devices, we can go down to individual cells and study their behavior in a controlled environment.”

“This model can be applied to far more than just physical cancer cells,” Moon continued. “Every cell can be influenced by different cues, and this provides researchers with a framework to study these influences and determine why they occur. Genetic engineers have also embraced the logic gate model, treating genes as processors that produce different results when you give them certain instructions. There are many areas where we can work with this concept.”

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