The mechanics of programmed cell death unravelled

A recent study has found a new triggering mechanism for programmed cell death (apoptosis). Unlike earlier known trigger mechanisms that involve chemicals being released by the cell destined for death, this is a physical mechanism. The study has found that a particular type of imperfection in the alignment of the cells appears to be correlated with the position of the cell destined to die. The results of the collaborative study was published in Nature.

The group has studied this correlation experimentally using five different kinds of epithelial tissue. Epithelial cells are those that line the outside and inside of our organs. These cells play a protective role and cells often undergo some kind of damage and need to be removed. This happens through a process of programmed cell death known as apoptosis. The cell destined for apoptosis is pushed out of the layer it inhabits in the epithelial tissue and then dies.

Cells in the epithelial layer usually are arranged neatly and regularly, like bricks on a wall, where the axes of the bricks are all aligned parallel to each other. But at times there is a defective alignment of the axes of the cells. Among the different types of defect, there is one where the tilt of the axes varies gradually — radiating out from a point, like a comet. The cell destined to die lies close to the head of the comet-shaped defect and is eventually pushed out of the layer of cells and apoptosis takes place.

Physics reasons

“The study tells you that it is not just biochemistry but physics, or precisely, mechanics, that can affect cell extrusions [the pushing out of cells from the layer they inhabit]. That means you may be able to think about situations where applying forces might make cells behave in a particular way,” says Sumesh Thampi from the Department of Chemical Engineering, IIT Madras, an author of the paper.

Collaborative study

While the theory and simulations were developed by members from Oxford, the experiments were carried out by groups from Singapore and the measurement of the force on the cells was done using techniques developed by a group from Paris. “It is hard to pinpoint the beginning of the work, it arose through discussions…and then we designed new simulations and experiments to test our ideas,” Julia Yeomans of The Rudolf Peierls Centre for Theoretical Physics, Oxford, and a Principal Investigator of the project told The Hindu in an email.

Traction force microscopy was used to measure and compute the pressure on individual cells in the monolayer.

“We developed an original way to compute the stresses inside cell colonies using statistical methods (Bayesian inference). The computation of such stresses has been done by only a few labs for cells migrating on substrates...” says Benoit Ladoux of CNRS and University Paris Diderot (France) and Mechanobiology Institute, Singapore, a Principal Investigator of the project.

Now that the link between mechanics and cell extrusion has been established, it is for future experiments to determine how external pressure can be used to control, for instance, the development of tumours and prevent them from spreading uncontrollably.

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