The Indian Institute of Science, Bengaluru

An interdisciplinary team of researchers from the Indian Institute of Science have uncovered how the stiffness of a cell’s microenvironment influences its form and function. The findings are expected to provide a better understanding of what happens to tissues during healing of wounds.

Scar formation

“Inefficient wound healing results in tissue fibrosis, a process that can cause scar formation and may even lead to conditions like cardiac arrest. Changes in the mechanical properties of tissues like stiffness also happen in diseases like cancer,” IISc said.

The research team was led by Prof. Namrata Gundiah from the Department of Mechanical Engineering and Prof. Paturu Kondaiah from the Department of Developmental Biology and Genetics.

Change in stiffness

In the study, published in Bioengineering, the team cultured fibroblast cells, the building blocks of our body’s connective tissue, on a polymer substrate called PDMS with varying degrees of stiffness.

They found that a change in the stiffness altered the cell structure and function. Fibroblast cells are involved in extensive remodelling of the extracellular matrix (ECM) surrounding biological cells.

The ECM, in turn, provides the mechanical tension that cells feel inside the body. The team found that fibroblasts cultured on substrates that had lower stiffness were rounder and showed accompanying changes in the levels of cytoskeleton proteins such as actin and tubulin. Moreover, fibroblasts grown on such substrates showed cell cycle arrest, lower rates of cell growth and cell death.

Regulator that drives changes

To pinpoint the master regulator that drives changes in the cell when substrate stiffness changes, the team focused their attention on an important signalling protein called Transforming Growth Factor-β (TGF-β). Previous work has shown that the activity of fibroblasts and the downstream ECM architecture is regulated by TGF-β.

“The thing is, people talk about the chemical changes but not about biomechanical changes. For example, while the TGF-β signalling cascade has been studied extensively in cancer, the influence of mechanical forces such as substrate stiffness has not been studied so far,” said Brijesh Kumar Verma, first author of the study. In the future, the researchers seek to understand how other mechanical factors, such as surface properties and cell stretch, can also influence TGF-β activity.