Cell removal as the result of a mechanical instability

June 19, 2020

The outer or inner boundaries of organs in the human body are lined with so-called epithelial sheets. These are layers of epithelial cells that can individually change their 3D shape -- which is what happens during biological processes like organ development (morphogenesis), physiological equilibrium (homeostatis) or cancer formation (carcinogenesis). Of particular interest is the process of cell extrusion, where a single cell loses its 'top' or 'bottom' surface and is subsequently pushed out of the layer. A thorough understanding of this phenomenon from a mechanical point of view has been lacking, but now, Satoru Okuda and Koichi Fujimoto from Kanazawa University have discovered that there is a purely mechanical cause for cell extrusion.

Mechanically speaking, a simple (single-layer) epithelial sheet is analogous to a foam, and can be represented as a layer of interconnected polyhedra. Okuda and Fujimoto used such a foam model to describe a monolayer of epithelial cells, with each cell a polyhedron with average volume V. Every cell is further characterized by the number of neighboring cells n, the area of the apical ('top') and the area of the basal ('bottom') surface. The model, taking into account mechanical forces between neighboring cells, leads to a formula for the total mechanical energy of an epithelial sheet as a function of only a few parameters, including V and n, as well as the in-plane density and a quantity called sharpness, which can distinguish between situations where basal and/or apical surfaces are present or not. (A vanished apical surface implies basal extrusion and vice versa.) By studying how the energy changes by varying these few parameters, the researchers were able to obtain valuable insights into the mechanics of an epithelial sheet.

The key finding of Okuda and Fujimoto is that the system exhibits an inherent mechanical instability: small changes in cell topology or cell density can cause cell extrusion without additional forces being applied. Furthermore, it turns out that a cell undergoing extrusion generates forces within the layer, which can direct the extrusion of other cells to either side of the layer.

The scientists also found many agreements between the outcomes of their model and observations in living systems, such as the occurrence of different epithelial geometries (e.g. 'rosette' or pseudostratified structures).

The model admittedly has limitations, for example the assumptions that the whole sheet and the individual cell surfaces are not curved but flat. However, quoting the researchers, "despite its limitations, [the] model provides a guide to understanding the wide range of epithelial physiology that occurs in morphogenesis, homeostasis, and carcinogenesis".

[Background]

Epithelial cells

Epithelial tissue, one of four kinds of human (or animal) tissue, is located on the outer surfaces of organs and blood vessels in the human body, and on the inner surfaces of 'hollow spaces' in various internal organs. A typical example is the outer layer of the skin, called the epidermis. Epithelial tissue consists of epithelial cells; it can be just one layer of epithelial cells (simple epithelium), or two or more (layered or stratified epithelium). Satoru Okuda and Koichi Fujimoto from Kanazawa University have now modeled a simple epithelium as an arrangement of polyhedra in order to study its mechanical properties and specifically the process of epithelial cell extrusion.

Cell extrusion

In epithelial tissue, cell extrusions happen -- the processes whereby epithelial cells are 'pushed out' of the epithelium. Cell extrusion is an important biological process, regulating for example the removal of apoptotic (dead) cells, tissue growth and the response to cancer. Okuda and Fujimoto looked at a simple epithelium from a mechanical point of view. Modeling the epithelium as a layer of interconnected polyhedra, they found that cell extrusion -- whereby the top or bottom surface of a polyhedron shrinks to a point and then vanishes -- can be considered a purely mechanical property. An inherent instability, present in homogeneous sheets, can lead to cells being extruded due to small changes in density or topology.
-end-


Kanazawa University

Related Epithelial Cells Articles from Brightsurf:

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Moffitt researchers identify protein that causes epithelial cancers to spread
In a new article published in the July issue of Cancer Research, Elsa Flores, Ph.D., and her team discovered a key protein that oscillates its expression through microRNA regulation to facilitate cancer spread to distant organs.

Epithelial GPS: Position of RNAi machinery is associated with epithelial identity
Researchers at the Medical University of South Carolina show in a new report that the RNA interference machinery, normally thought to reside in the nucleus or cytoplasm, predominantly localizes to these apical junctions and influences cell biology in the colon.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Scientists modify CAR-T cells to target multiple sites on leukemia cells
In a preclinical study, scientists engineer new CAR-T cells to attack three sites on leukemia cells, instead of one.

Size matters: How cells pack in epithelial tissues
Small-cell clones in proliferating epithelia -- tissues that line all body surfaces -- organize very differently than their normal-sized counterparts, according to a recent study from the Stowers Institute for Medical Research.

Closing the gap -- a two-tier mechanism for epithelial barrier
Scientists from Japan's National Institute for Physiological Sciences and their collaborators report in a new study published in The Journal of Cell Biology that epithelial barrier is composed of two molecular systems with distinct barrier properties.

Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.

Revealed: How the 'Iron Man' of immune cells helps T cells fight infection
The immune system's killer T cells are crucial in fighting viral infections.

White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.

Read More: Epithelial Cells News and Epithelial Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.