One study found that crowded cells form concentric circles by slowing their growth.Scott Weady's team's model helps manage the growth of harmful microorganisms. Like many other organisms, cells become stressed when they are crowded with a hodgepodge of cells. However, unlike other life forms, when cells are physically stressed by their crowded neighbors, they can relieve the stress by dramatically slowing their growth rates, forming beautiful patterns of concentric circles in the process.
A new study published in Physical Review Letters describes the discovery by simulating and modeling dividing bacterial colonies. The insights could provide new strategies for slowing the growth of harmful microorganisms during infections or manufacturing processes, said Scott Weady, the study's first author and a researcher at the Flatiron Institute's Center for Computational Biology in New York City.
"I was really surprised to see how the cells could slow down their growth under such mechanical stress," said Vedi. "What's interesting is that they form these concentric circles, and each ring shows how much they are being smothered by the cells around them, which ultimately affects how big they can grow. It's a powerful pattern that comes from a very simple rule, it's just that no one had really thought to measure it before."
Wade co-authored the study with Flatiron Institute researchers Bryce Palmer, Adam Lamson, Reza Farhadifar, and Michael Shelley, as well as Purdue University's Taeyoon Kim.
Wade's research group is interested in biophysical modeling, or, in his words, studying how small-scale rules govern large-scale behavior. In this case, his team wanted to study cell proliferation, the process by which cells divide to make more copies.
The team started with an exploratory approach to simulate the growth of bacterial colonies. At first, they looked at more general measures such as cell size regulation, but then began to notice a pattern.
Normally, cells multiply exponentially: One cell splits in two, and those offspring split in two, and so on, multiplying at an ever-increasing rate. However, in their simulations, the team noticed that the cells didn't divide as you'd expect - in fact, the cells' proliferation slowed down significantly as the environment they found became more crowded.
"You start with one cell, and it feels almost no pressure. Then it divides, and those cells divide, and the cells closer to the center get more and more stressed because there's more pressure on them, and that causes them to grow slower, so as you move toward the edges of the circle, you get these non-uniform stress-sensitive bands that appear as concentric circles."
The initial work was based on particle simulations that illustrated how the proliferation process proceeds in a relatively small number of cells. On the basis of this data, the research team developed a so-called continuum model that can estimate how the proliferation process proceeds in extremely large numbers of cells.
"In particle simulations you see something discrete - in this case you're tracking bacteria over time. But the continuum model operates differently in that it assumes that the number of particles is very large so it can be represented as a continuous material. This helps us better study this process on a larger scale and understand its robustness," said Vedi.
Excitingly, the team found that their continuum model matched closely with what they saw in particle simulations, suggesting that their hunch was correct: cornered cells slow their own growth, creating a stasis pattern in the process.
Cell proliferation is an extremely valuable research topic because it is a very fundamental process, but also because when the proliferating cells are harmful (such as bacterial infections), they can cause harmful effects.
"It's really important to figure out how this process is naturally regulated and how it's controlled," said Wade. "Our model identifies environmental factors that can enhance a cell's response to mechanical stress, and promoting these factors can slow exponential growth. I think this model is a useful tool to help people study perturbations in the way cells respond, whether through stress, nutrient access, or other means. It's very clear how to ask these questions with a model like this, so I think it's exciting because it will enable this on a broader scale."
The model developed in this study could also serve as a basis for studying other cell behaviors.
Compiled from/SciTechDaily