Review of “Cell mechanosensing is regulated by substrate strain energy rather than stiffness”.

April 15, 2021

 Puranjan Ghimire
Department of Physics
Nano Literature Seminar
Virginia Commonwealth University

Thursday, April 15 at 11:00 am via Zoom

Cell mechanosensing is regulated by substrate strain energy rather than stiffness. V. Panzetta, S. Fusco, and P.A. Netti. PNAS, 116, 22004-22013 (2021)


Cells can adapt to not only biological or chemical cues but also physical cues by a process called mechanosensing. For example, mechanical properties of extra cellular matrix (ECM) significantly influence the biochemical activities of the cell [1], and the elasticity of ECM [2] can impact the differentiation of the cell into various cell types – muscle cells, bone cells, or brain cells. This paper is to test the long-lasting debate whether the cell is sensitive to stiffness or the strain energy required to deform the ECM. The role of strain energy of the substrate toward cell mechanosensing was studied by seeding two murine cell types BALB/T3T and MC3T3 on linearly elastic substrates. Cells were seeded on substrates in two different ways. In the first way, the cells were seeded in stretched substrate and secondly cells were seeded in unstretched substrate and then stretched to two different levels of deformation. The authors report that i) cells seeded on stretched substrate exhibit stiffer cytoskeleton than cells seeded on unstretched substrate, and ii) cells seeded on stretched material and cells stretched with substrate exhibited similar cytoskeleton mechanics. These two observations suggest that the substrate strain energy is the key cell mechanosensing regulatory in addition to substrate stiffness. The traditional motor-clutch model which is based on the cell mechanosensing of substrate stiffness fails to describe the experimental observation. However, the inclusion of substrate strain energy into the model produces the simulation result in accordance with experimental observations.

[1] T Iskratsch, H Wolfenson and M P Sheetz, Appreciating Force and Shape – The Rise of Mechanotransduction in Cell Biology, Nature Rev. Mol Cell Biol., Vol.12, pp.825–833, 2014.
[2] D E Discher, P Janmey and Y L Wang, Tissue Cells Feel and Respond to the Stiffness of Their Substrate, Science, Vol.18, pp.1139–1143, 2005.


 Puranjan Ghimire is a Ph.D. student in nanoscience at the Virginia Commonwealth University.