Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation

In the field of mechanobiology, it has been very well established that mechanical properties of cellular micro-environment provides a significant contribution towards cellular behaviour. One of the major player in mechanobiology is material’s stiffness. It has been proved that, when cells are seeded on a hard substrate, they spread more and become flat as compared to soft material where they almost remain round. However, this property has been studied with sparsely seeded cells, on contrary to in-vivo where cells are not distantly apart but in close contact with each other. When we decreased the inter-cellular distance on soft substrate, the cells, instead of remaining round started to spread and elongated towards their nearest neighbour. Further investigation revealed an active involvement of cell in deforming the soft matrix. This deformation was sensed by the neighbouring cell. In response to this deformation, the neighbouring cell applied a counteracting force to resist the deformation. This tug of war between cells lead to localized increase in material’s stiffness. This material stiffness was then sensed by the cells and as a result they begin to spread. Thus at higher seeding density or decreased inter-cellular distance, cells behave as being cultured on stiff matrix despite of being on a soft substrate via localized increased stiffness.

Publication details: Venugopal, Balu, Pankaj Mogha, Jyotsna Dhawan, and Abhijit Majumder. 2018. "Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation". Biomaterials Science. 6 (5): 1109-1119.



  • Wellcome Trust-DBT India Alliance (Project # IA/E/11/1/500419)
  • Seed grant from IITB (Grant # 14IRCCSG002) and core grants from the Dept of Biotechnology to inStem.
  • Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White through a grant from NCRR of the NIH, grant # P40RR017447.
  • IRCC, IIT Bombay Bio-AFM and confocal microscopy facility.
  • Dr James P Butler (Harvard Medical School, Department of Medicine, Boston)