A novel approach for extracting viscoelastic parameters of living cells through combination of inverse finite element simulation and Atomic Force Microscopy

Comput Methods Biomech Biomed Engin. 2017 Mar;20(4):373-384. doi: 10.1080/10255842.2016.1233403. Epub 2016 Sep 14.

Abstract

Dynamic mechanical behaviour of living cells has been described by viscoelasticity. However, quantitation of the viscoelastic parameters for living cells is far from sophisticated. In this paper, combining inverse finite element (FE) simulation with Atomic Force Microscope characterization, we attempt to develop a new method to evaluate and acquire trustworthy viscoelastic index of living cells. First, influence of the experiment parameters on stress relaxation process is assessed using FE simulation. As suggested by the simulations, cell height has negligible impact on shape of the force-time curve, i.e. the characteristic relaxation time; and the effect originates from substrate can be totally eliminated when stiff substrate (Young's modulus larger than 3 GPa) is used. Then, so as to develop an effective optimization strategy for the inverse FE simulation, the parameters sensitivity evaluation is performed for Young's modulus, Poisson's ratio, and characteristic relaxation time. With the experiment data obtained through typical stress relaxation measurement, viscoelastic parameters are extracted through the inverse FE simulation by comparing the simulation results and experimental measurements. Finally, reliability of the acquired mechanical parameters is verified with different load experiments performed on the same cell.

Keywords: Atomic Force Microscopy; Viscoelasticity; finite element simulation.

MeSH terms

  • Cell Survival
  • Computer Simulation*
  • Elastic Modulus
  • Elasticity*
  • Finite Element Analysis*
  • HEK293 Cells
  • Humans
  • Microscopy, Atomic Force / methods*
  • Models, Biological
  • Reproducibility of Results
  • Stress, Mechanical
  • Viscosity