WP1

WP1

 Mechanical Model of whole Cell

The aim of the research is to develop novel constitutive laws and multiscale models of cytoskeletal network dynamics. 

Project 1: We will develop a type of free energy function to describe a whole cell by including the fibre (actin) dispersion, various filaments within the cell cytoskeleton and other constituents (e.g. the nucleus), viscoelastic properties of the cell, and the cell membrane. 

Project 2: We will also extend the cell model to describe how mechanical and chemical stimuli influence protein expression and thus cell functionality and Growth&Remodelling of the extracellular matrix (thorough interaction with WP2) for matrix remodelling post myocardial infarction and cancer invasion.

 

Team: Prof.Ogden (leader), Dr. Yin, Prof. Olson, Prof. Chaplain, Prof. Insall, Prof. Husiemer, Prof. Luo, PDRA1, PhD1  

 

WP1 Summary

We have developed a multiscale model for an individual cell that incorporates the mechanical properties of the separate cell constituents in order to characterize the overall mechanical response of the whole cell by using a homogenization method based on volume averaging over the cell domain. The method has been applied to a prototype spherical cell consisting of a soft neo-Hookean material within a spherical shell composed of randomly distributed fibres representing the F-actin cortex. A material subroutine for a fibre-reinforced model has been implemented within the FE software FEAP. To understand the data from Atomic Force Microscopy (AFM) indentation conducted within the experimental part of the project, we have simulated a variety of simple contact problems in FEAP, with different material models and shapes of the indenters.

The experiments make use of AFM for measuring cell mechanical properties and cell-matrix interactions. Recently, we have developed a novel AFM-microrheology technique to obtain viscoelastic properties of cells and complex materials, over a wide range of continuous frequencies (0.003 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation (see figure for the a schematic of the experimental setup). Using this capability, we were able to investigate the viscoelastic responses of cells in association with cancer cell invasion. In addition, we are developing peptide hydrogels with tunable chemical and mechanical properties. This will allow further studies to be carried out in controlled 3D environments that mimic natural extracellular matrix. 

Final WP1 Figure