Unlocking the secrets of cellular shape-shifting

21 December 2023

Cells and tissues are known to undergo significant plastic deformations during many biological processes such as cell migration, tissue regeneration, organ development and growth, cancer metastasis, and morphogenesis. Until now we have not had a comprehensive theory of how this happens.

Professor Yuan Lin of the Department of Mechanical Engineering at the University of Hong Kong and his colleagues including researchers at the Nanyang Technological University in Singapore have developed a mechanism-based theory of cellular and tissue plasticity that accounts for the key processes involved and achieves quantitative agreement with existing experiments. The theory shows how plasticity is initiated in individual cells and then propagates within tissues.

Lin and his team showed that when cells are stimulated by light or physical pressure, a protein called myosin helps the cells to contract and this combined with normal temperature-related movements within the cells can cause the formation of the small bubbles, known as endocytic vesicles. These vesicles can make the connections between cells permanently shorter. When one cell contracts it can pull on adjacent cells causing them to also contract and deform. The theory suggests that stimulating the cells in short bursts rather than one long stretch, results in more of these permanent changes. Experimental data supports this concept.

Cellular plasticity across different scales. (A) Schematics showing that 1) the collective plastic response of cells leads to tissue plasticity at macroscopic scales; 2) formation and scission of membrane vesicles result in irreversible deformation of individual cells; 3) various proteins participate in the initiation and pinching of endocytic vesicles at the subcellular scale. (B) Illustration of the multiscale model where cells are treated as tightly packed hexagons at the tissue level; cell-cell junctions are modelled as springs connecting corresponding vertices at the cellular level; and the activation of signalling molecules (triggered by optical/mechanical stimuli), as well as recruitment of myosin motors to the cell junction, are considered at the subcellular scale. (C) Summary of key processes involved in the development of cellular and tissue plasticity. Image: Lin et al, HKU

The team also described a point after which the changes in cells go from being temporary to permanent. Once this happens, the defomration can spread through the tissue like a wave at a constant speed, a behaviour that has also been seen in experiments. The findings were published in the Proceedings of the National Academy of Sciences.