Novel insights into cell-cell mechanical interactions that can be employed in tissue engineering
02 Apr 2018
Indian Institute of Technology (IIT) Bombay
Different parts of our body have different stiffness. While influence of these varied stiffness on our wellbeing is obvious in some situations, such as muscle has to be soft to provide flexibility whereas bone has to be rigid to provide structural integrity, effect of tissue stiffness on cellular behavior is much more widespread. Adherent cells measure the stiffness of their micro-environment by holding and pulling the surrounding materials and respond accordingly. For example, studies with mesenchymal stem cells (MSCs) or “adult” stem cells have shown that they do not divide when grown on soft materials. Substrate stiffness also controls whether a stem cell would become nerve cell or muscle cell or something else. Other than that, tissue stiffness is known to influence metastasis and drug resistance in cancer.
However, most of these observations are made when cells are cultured at sparse keeping them away from each other. This is very different from the situation in our body where cells are much more closely spaced. What happens when cells are so close that pulling by one cell is felt by its neighbor?
Our research has found that as we reduce the distance between two cells on soft substrate (such as polyacrylamide gel), they together can make the substrate stiff simply by pulling it in two opposite direction similar to making a flexible rope taut in tug of war. This way, together they can overcome the effect of soft surface. For instance, even though many adherent cells cannot divide when on soft substrate, together they can overcome this effect of soft surface on cell division. Another interesting observation was that they together form a network holding "hand in hand" to provide sufficient support for each other which is lacking on a soft surrounding.
The knowledge gained in this research is useful in tissue engineering and discovering newer treatment strategies in addition to enhancing our understanding of how cells work together in our body.
Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation. Balu Venugopal, Pankaj Mogha, Jyotsna Dhawan and Abhijit Majumder. Biomaterials Science. March 2018