Using Cancer Cells as Logic Gates to Determine What Makes Them Move – ScienceDaily


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

For many years, professor of mechanical engineering Pomsoo Han and his research group have been studying cancer cells. 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 have been observing and studying how these cancer cells migrate, because it is an important aspect of cancerous metastasis,” said Hy Ran Moon, a postdoctoral researcher in Han’s team. “But this is different. We are trying to address the underlying mechanisms behind these behaviors. Which is very difficult because cells are very complex systems of molecules, and they are exposed to multiple signals that make them move.”

One of these signals involves chemical pathways, which many cells are attracted to (like ants following a scent trail). Another is fluid flow. If fluids flow around the cells in a certain direction, many cells will travel along the way. So if a cell is moving, how do you tell if it’s being stimulated by chemicals, fluid movements, or both?

The team adopted the triple logic gate model to analyze these signals, and to predict how cells would move in different environments. Their research has been published in lab on a chipJournal of the Royal Society of Chemistry.

Their experiments were carried out in a microfluidic platform with a central chamber for cells and two lateral platforms. With this device, they can replicate liquid flows in one direction, in the opposite direction, or no flow at all. They can also introduce a chemical known to cause cell migration. Again, they had the choice of chemotaxis in one direction, in the opposite direction, or none at all. Do these signals reproduce or cancel each other out?

“With two signals and three options each, we had enough observable data to build a three-way logic gate model,” Moon said.

Logic gates are a construct of computing, where transistors take a 1 or 0 as an input and return an output of 1 or 0. Binary logic gates take a combination of two 1’s and a 0’s, and output different results depending on the type of gate. Triple logic gates do the same thing, except there are three possible inputs and outputs: 1, 0, and -1.

The moon set values ​​for the direction in which the cells moved under the two different stimuli. “If the cells move in the direction of flow, that equals 1,” Moon said. “If they have no direction, that’s 0. If they move in the opposite direction of the flow, that’s -1.”

When cells encounter individually flowing chemicals or fluids, they move in the positive (“1”) direction. When both were located in the same direction, the effect was additive (still “1”). However, when the two flow in opposite directions, the cells move in the direction of the chemicals (“-1”), rather than the flow of fluids.

Based on these observations, Moon stabilized a 3×3 grid to simplify the results. The signals of these cancer cells can now be plotted schematically much like an electrical engineer drawing a circuit.

Of course, the real world is never that simple. “Actually, chemical stimulation is a gradient, not an on-and-off switch,” Moon said. “Cells will only move once a certain threshold of flow is entered; if you introduce too much, the cell short circuits not to move at all. The precision with which we can predict movement is a nonlinear relationship.”

Moon also emphasized that this particular experience is very simple: two stimuli, in diametrically opposite directions, in one dimension. The next step would be to build a similar experience, but in a two-dimensional plane; Then another in 3D volume. And that’s just for starters. Once you add in multiple stimuli, and factor in time as the fourth dimension, the calculations become incredibly complex. “Now you understand why biologists need to use supercomputers!” said the moon.

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

“This is a great example of how microfluidic devices can be used in cancer research,” Moon said. “Doing this experiment in a biological environment would be very challenging. But with these devices, we can go directly to individual cells and study their behavior in a controlled environment.”

“This model could apply to more than just physical cancer cells,” Moon continued. “Any cell can be affected by different signals, and this provides a framework for researchers to study those effects and determine why they occur. Genetic engineers have also adopted the logic-gate model, treating genes as processors that give different results when you give them some instruction. There are many branches we can follow. with this concept.



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