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Experimental and computational assessment of F-actin influence in regulating cellular stiffness and relaxation behaviour of fibroblasts
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).ORCID iD: 0000-0002-6388-0995
KTH, School of Engineering Sciences (SCI), Applied Physics.
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Fibre Technology.ORCID iD: 0000-0002-5444-7276
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
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2016 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 59, 168-184 p.Article in journal (Refereed) Published
Abstract [en]

In biomechanics, a complete understanding of the structures and mechanisms that regulate cellular stiffness at a molecular level remain elusive. In this paper, we have elucidated the role of filamentous actin (F-actin) in regulating elastic and viscous properties of the cytoplasm and the nucleus. Specifically, we performed colloidal-probe atomic force microscopy (AFM) on BjhTERT fibroblast cells incubated with Latrunculin B (LatB), which results in depolymerisation of F-actin, or DMSO control. We found that the treatment with LatB not only reduced cellular stiffness, but also greatly increased the relaxation rate for the cytoplasm in the peripheral region and in the vicinity of the nucleus. We thus conclude that F-actin is a major determinant in not only providing elastic stiffness to the cell, but also in regulating its viscous behaviour. To further investigate the interdependence of different cytoskeletal networks and cell shape, we provided a computational model in a finite element framework. The computational model is based on a split strain energy function of separate cellular constituents, here assumed to be cytoskeletal components, for which a composite strain energy function was defined. We found a significant influence of cell geometry on the predicted mechanical response. Importantly, the relaxation behaviour of the cell can be characterised by a material model with two time constants that have previously been found to predict mechanical behaviour of actin and intermediate filament networks. By merely tuning two effective stiffness parameters, the model predicts experimental results in cells with a partly depolymerised actin cytoskeleton as well as in untreated control. This indicates that actin and intermediate filament networks are instrumental in providing elastic stiffness in response to applied forces, as well as governing the relaxation behaviour over shorter and longer time-scales, respectively.

Place, publisher, year, edition, pages
Elsevier, 2016. Vol. 59, 168-184 p.
Keyword [en]
Actin, relaxation, constitutive
National Category
Research subject
Solid Mechanics; Biological Physics
URN: urn:nbn:se:kth:diva-173937DOI: 10.1016/j.jmbbm.2015.11.039ScopusID: 2-s2.0-84952934669OAI: diva2:856364
Swedish Research Council, A0437201

Updated from "Manuscript" to "Article". QC 20160201

Available from: 2015-09-24 Created: 2015-09-24 Last updated: 2016-02-01Bibliographically 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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Fallqvist, BjörnFielden, MatthewPettersson, TorbjörnNordgren, NiklasKroon, Martin
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