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Biological materials can undergo large deformations and also show viscoelastic behaviour. One such material is the network of actin filaments found in biological cells, giving the cell much of its mechanical stiffness. A theory for predicting the relaxation behaviour of actin networks cross-linked with the cross-linker α-actinin is proposed. The constitutive model is based on a continuum approach involving a neo-Hookean material model, modified in terms of concentration of chemically activated cross-links. The chemical model builds on work done by Spiros (Doctoral thesis, University of British Columbia, Vancouver, Canada, 1998) and has been modified to respond to mechanical stress experienced by the network. The deformation is split into a viscous and elastic part, and a thermodynamically motivated rate equation is assigned for the evolution of viscous deformation. The model predictions were evaluated for stress relaxation tests at different levels of strain and found to be in good agreement with experimental results for actin networks cross-linked with α-actinin.

Abstract:The actin cytoskeleton is essential for the continued function and survival of the cell. A peculiar mechanical characteristic of actin networks is their remodelling ability, providing them with a time-dependent response to mechanical forces. In cross-linked actin networks, this behaviour is typically tuned by the binding affinity of the cross-link. We propose that the debonding of a cross-link between filaments can be modelled using a stochastic approach, in which the activation energy for a bond is modified by a term to account for mechanical strain energy. By use of a finite element model, we perform numerical analyses in which we first compare the model behaviour to experimental results. The computed and experimental results are in good agreement for short time scales, but over longer time scales the stress is overestimated. However, it does provide a possible explanation for experimentally observed strain-rate dependence as well as strain-softening at longer time scales.

Cells are known to respond over time to mechanical stimuli, even actively generating force at longer times. In this paper, a microstructural filament-based cytoskeletal network model is extended to incorporate this active response, and a computational study to assess the influence on relaxation behaviour was performed. The incorporation of an active response was achieved by including a strain energy function of contractile activity from the cross-linked actin filaments. A four-state chemical model and strain energy function was adopted, and generalisation to three dimensions and the macroscopic deformation field was performed by integration over the unit sphere. Computational results in MATLAB and ABAQUS/Explicit indicated an active cellular response over various time-scales, dependent on contractile parameters. Important features such as force generation and increasing cell stiffness due to prestress are qualitatively predicted. The work in this paper can easily be extended to encompass other filament-based cytoskeletal models as well.