Study offers insights into cell functioning during wound healing

Do tissues in the body undergo changes in its properties when a disease like cancer strikes? Similarly, why does a wound heal at different rates in different tissues?

These are a few questions being answered by an interdisciplinary team of researchers at the Indian Institute of Science (IISc), which has said that different tissues have different levels of stiffness — from being soft around muscles, to very hard around bones.

This, it said, was because the Extra Cellular Matrix (ECM) surrounding different tissues has different levels of stiffness.

This team has come up with a few findings after successfully monitoring how the stiffness of a cell’s micro-environment influences its form and function. The findings provide a better understanding of tissues during wound healing.

In the study, published in peer-reviewed journal Bioengineering, the researchers cultured fibroblast cells — the building blocks of the human body’s connective tissue — on a polymer substrate called PDMS, with varying degrees of stiffness.

The team — led by Namrata Gundiah, Professor at the Department of Mechanical Engineering, and Paturu Kondaiah, Professor at the Department of Developmental Biology and Genetics — found that changes in the stiffness also altered cell structure and function. Fibroblasts cultured on substrates with lower stiffness showed cell cycle arrest, lower rates of cell growth, and cell death.

The researchers found that with increasing substrate stiffness, the levels of Transforming Growth Factor-β (TGF-β), an important signalling protein, also started rising.

Brijesh Kumar Verma, former PhD student at the Department of Developmental Biology and Genetics, IISc, and first author of the study, said that this could explain why wound healing occurs at different rates in different tissues — bone tissues that grow on a stiffer ECM may be less prone to scarring upon injury when compared to muscle tissues that reside in a softer biomechanical environment.

Changes in the mechanical properties of tissues like stiffness also happen in diseases like cancer. “A tumour mass can be targeted more efficiently if we understand how stiffness changes in diseased cells,” Verma said.

Understanding the influence of different forces on the micro-environment of the cell and tracking the cell’s biophysical parameters can help distinguish between healthy and cancer cells, IISc noted. The team also found that there was an uptick in the production of several ECM components when the substrate stiffness increased.