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Implementing cell contractility in filament-based cytoskeletal models
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).ORCID iD: 0000-0002-6388-0995
2016 (English)In: Cytoskeleton, Vol. 73, no 2, 12 p.93-106 p.Article in journal (Other (popular science, discussion, etc.)) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016. Vol. 73, no 2, 12 p.93-106 p.
Keyword [en]
Contractility, cell, constitutive, actin, cytoskeleton
National Category
Biophysics Materials Engineering
Research subject
Biological Physics; Solid Mechanics
URN: urn:nbn:se:kth:diva-175408DOI: 10.1002/cm.21279ISI: 000371414800004PubMedID: 26899417ScopusID: 2-s2.0-84959460849OAI: diva2:860834

Updated from submitted to published.

QC 20160311. QC 20160407

Available from: 2015-10-14 Created: 2015-10-14 Last updated: 2016-04-07Bibliographically approved
In thesis
1. On the mechanics of actin and intermediate filament networks and their contribution to cellular mechanics
Open this publication in new window or tab >>On the mechanics of actin and intermediate filament networks and their contribution to cellular mechanics
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mechanical behaviour of cells is essential in ensuring continued physiological function, and deficiencies therein can result in a variety of diseases. Also, altered mechanical response of cells can in certain cases be an indicator of a diseased state, and even actively promoting progression of pathology. In this thesis, methods to model cell and cytoskeletal mechanics are developed and analysed.

In Paper A, a constitutive model for the response of transiently cross-linked actin networks is developed using a continuum framework. A strain energy function is proposed and modified in terms of chemically activated cross-links.

In Paper B, a finite element framework was used to assess the influence of numerous geometrical and material parameters on the response of cross-linked actin networks, quantifying the influence of microstructural properties and cross-link compliance. Also, a micromechanically motivated constitutive model for cross-linked networks in a continuum framework was proposed.

In Paper C, the discrete model is extended to include the stochastic nature of cross-links. The strain rate dependence observed in experiments is suggested to depend partly on this.

In Paper D, the continuum model for cross-linked networks is extended to encompass more composite networks. Favourable comparisons to experiments indicate the interplay between phenomenological evolution laws to predict effects in biopolymer networks.

In Paper E, experimental and computational techniques are used to assess influence of the actin cytoskeleton on the mechanical response of fibroblast cells. The influence of cell shape is assessed, and experimental and computational aspects of cell mechanics are discussed.

In Paper F, the filament-based cytoskeletal model is extended with an active response to predict active force generation.  Importantly, experimentally observed stiffening of cells with applied stress is predicted.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. 68 p.
TRITA-HFL. Report / Royal Institute of Technology, Solid Mechanics, ISSN 1654-1472 ; 0583
actin, cell, mechanical, constitutive, intermediate, continuum, constitutive
National Category
Applied Mechanics
Research subject
Solid Mechanics
urn:nbn:se:kth:diva-175748 (URN)978-91-7595-752-4 (ISBN)
Public defence
2016-01-29, Kollegiesalen, Brinellvägen 8, Stockholm, 10:00 (English)
Swedish Research Council, A0437201

QC 20151209

Available from: 2015-12-09 Created: 2015-10-20 Last updated: 2015-12-09Bibliographically approved

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