Top row: A transition from normal epithelial cells in a honeycomb pattern (top left) to shifted cells. This transition leads to increasing disorder in their shapes. Bottom row: Simulated patterns from the theoretical vertex model recapitulate cell shapes and topologies.

These Cells Protect Your Organs, but Cancer May Send Them Running. Here’s a Theory Why.

From keeping out pathogenic invasions, to buffering blunt force trauma, epithelial cells have an important job: standing on the front line to keep your organs safe. But what happens when circumstances like embryonic development or cancer cause these cells to behave differently?

As principal investigator of the Theoretical Soft Matter and Biophysics Group and an Assistant Professor of Physics, Dr. Max Bi was naturally curious. Alongside Le Yan of University of California, Santa Barbara, their paper titled “Multicellular Rosettes Drive Fluid-solid Transition in Epithelial Tissues” sought to investigate the mysterious nature of these tissue state transitions.

Assistant Professor of Physics Max Bi helped develop a model of cell behavior, explaining why certain conditions cause epithelial cells to transition from a solid to a fluid-like state. Photo by Matthew Modoono/Northeastern University

They knew that, by default, the cells in these epithelial tissues are sedentary, resembling solid matter. It’s only when confronted with conditions like embryonic development, tissue repair, and cancer invasion that these cells may become migratory, and potentially even fluid-like.

Because these conditions are essential to growth and survival, Bi and Yan wanted to better understand the mechanism behind this transition from stationary to fluid tissue, which could have a significant impact on scientific comprehension of development, medicine, and disease progression.

Published by the American Physical Society in the prestigious journal Physical Review X, their article describes a theoretical model of cellular organization that incorporates complex junctions between cells and analyzes their influence on the fluidity of the tissues they compose.

To analyze these junctions, the authors specifically studied multicellular rosettes. As one would expect from its name, a rosette is a conglomeration of cells, defined by its vertices of five or more

cells, that are shaped like a rose. Rosettes are often found in embryonic and morphological settings and are experimentally known to be significant in remodeling and growth in Drosophila embryos.

In their studies, the authors concluded that the level of tissue fluidity is dependent on the density of junctions with higher-order vertices, such as rosettes. Increased concentration of rosettes within an area would therefore result in increased rigidity, while decreased concentration would have the opposite effect. This theory of cell behavior takes into account several complex factors that previous models did not, resulting in a more comprehensive and experimentally sound model of theoretical cell behavior.

Dr. Bi is optimistic about the impact of his publication, stating that the ”theory predicts that rosettes are responsible for rigidifying a tissue and can act as locations that concentrate mechanical forces. [Therefore], this article will have an immediate impact in biology and bioengineering.” This impact may include, but is certainly not limited to, understanding crucial aspects of physiology and pathophysiology, from embryonic morphology in fruit flies to metastasis of cancer in humans.

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Physics