More cells = more movement
New research from the Queensland University of Technology (QUT) has revealed that cell movement actually increases when there are more cells around, contrary to what scientists have always believed.
The motivation for the study, published in the Journal of the Royal Society Interface, was to test some new mathematical models the QUT team had recently developed — models which were ideally suited to explore cell biology experiments. Such experiments are commonly used as screening tools to understand potential drug treatments, or different physical treatments like different surface coatings.
The team used advanced mathematical modelling and statistical analysis on a common experiment used by biologists known as a scratch assay. Cells (in this case, prostate cancer cells) are placed in a well, and then a scratch is made to create a large vacant region that separates the cells. Scientists then observe how the cell population grows and cells move to fill up that space.
Typical experimental protocols do not vary the initial cell density, or the initial number of cells that are used. Alex Browning, a PhD student at QUT and lead author of the study, wanted to change this.
“We wanted to explore how cell density affected the dynamics of the experiment by quantifying this,” Browning said. “Our mathematical and statistical methods allowed us to identify the nature of cell-to-cell interactions in the experiments that might lead to density-dependent behaviour.”
Cell biologists and mathematicians have always assumed that cell movement, or motility, is independent of density and not affected by cell-to-cell interactions. As noted by QUT Professor Matthew Simpson, who supervised the project, “Scientists in the past have thought of cells like people. The more space you’ve got, the easier it is to move. Turns out, it is more complicated than that.”
“Our results showed the opposite of what has always been assumed,” Browning added. “It turns out, a higher density environment where there are more cell-to-cell interactions actually increased cell movement.
“We were quite surprised.”
QUT mathematical biologist Dr Wang Jin, who co-authored the study, said the results were significant.
“Biologists do all sorts of in vitro experiments, where they grow cells in the lab, but there is no standard protocol that tells them how many cells they should put into the well to run their experiment,” Dr Jin said. “Our results show that it matters how many cells they use.”
Prof Simpson said the results also have implications for mathematicians, noting, “People often don’t change things. The simplest thing we have done here is to change the initial number of cells.
“By changing some of the most fundamental features of these experiments, which is so basic that no-one ever questions, we actually learn an awful lot.”
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