A multi-structural single cell model of force-induced interactions of cytoskeletal components

Sara Barreto, Casper Hyttel Clausen, Cecile M. Perrault, Daniel A. Fletcher, Damien Lacroix

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Several computational models based on experimental techniques and theories have been proposed to describe cytoskeleton (CSK) mechanics. Tensegrity is a prominent model for force generation, but it cannot predict mechanics of individual CSK components, nor explain the discrepancies from the different single cell stimulating techniques studies combined with cytoskeleton-disruptors. A new numerical concept that defines a multi-structural 3D finite element (FE) model of a single-adherent cell is proposed to investigate the biophysical and biochemical differences of the mechanical role of each cytoskeleton component under loading. The model includes prestressed actin bundles and microtubule within cytoplasm and nucleus surrounded by the actin cortex. We performed numerical simulations of atomic force microscopy (AFM) experiments by subjecting the cell model to compressive loads. The numerical role of the CSK components was corroborated with AFM force measurements on U2OS-osteosarcoma cells and NIH-3T3 fibroblasts exposed to different cytoskeleton-disrupting drugs. Computational simulation showed that actin cortex and microtubules are the major components targeted in resisting compression. This is a new numerical tool that explains the specific role of the cortex and overcomes the difficulty of isolating this component from other networks in vitro. This illustrates that a combination of cytoskeletal structures with their own properties is necessary for a complete description of cellular mechanics.
Original languageEnglish
JournalBiomaterials
Volume34
Issue number26
Pages (from-to)6119-6126
ISSN0142-9612
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Cytoskeleton
  • Finite element modeling
  • Actin cortex
  • Actin bundles
  • Microtubules
  • AFM (atomic force microscopy)

Cite this

Barreto, S., Clausen, C. H., Perrault, C. M., Fletcher, D. A., & Lacroix, D. (2013). A multi-structural single cell model of force-induced interactions of cytoskeletal components. Biomaterials, 34(26), 6119-6126. https://doi.org/10.1016/j.biomaterials.2013.04.022
Barreto, Sara ; Clausen, Casper Hyttel ; Perrault, Cecile M. ; Fletcher, Daniel A. ; Lacroix, Damien. / A multi-structural single cell model of force-induced interactions of cytoskeletal components. In: Biomaterials. 2013 ; Vol. 34, No. 26. pp. 6119-6126.
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Barreto, S, Clausen, CH, Perrault, CM, Fletcher, DA & Lacroix, D 2013, 'A multi-structural single cell model of force-induced interactions of cytoskeletal components', Biomaterials, vol. 34, no. 26, pp. 6119-6126. https://doi.org/10.1016/j.biomaterials.2013.04.022

A multi-structural single cell model of force-induced interactions of cytoskeletal components. / Barreto, Sara; Clausen, Casper Hyttel; Perrault, Cecile M.; Fletcher, Daniel A.; Lacroix, Damien.

In: Biomaterials, Vol. 34, No. 26, 2013, p. 6119-6126.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - A multi-structural single cell model of force-induced interactions of cytoskeletal components

AU - Barreto, Sara

AU - Clausen, Casper Hyttel

AU - Perrault, Cecile M.

AU - Fletcher, Daniel A.

AU - Lacroix, Damien

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AB - Several computational models based on experimental techniques and theories have been proposed to describe cytoskeleton (CSK) mechanics. Tensegrity is a prominent model for force generation, but it cannot predict mechanics of individual CSK components, nor explain the discrepancies from the different single cell stimulating techniques studies combined with cytoskeleton-disruptors. A new numerical concept that defines a multi-structural 3D finite element (FE) model of a single-adherent cell is proposed to investigate the biophysical and biochemical differences of the mechanical role of each cytoskeleton component under loading. The model includes prestressed actin bundles and microtubule within cytoplasm and nucleus surrounded by the actin cortex. We performed numerical simulations of atomic force microscopy (AFM) experiments by subjecting the cell model to compressive loads. The numerical role of the CSK components was corroborated with AFM force measurements on U2OS-osteosarcoma cells and NIH-3T3 fibroblasts exposed to different cytoskeleton-disrupting drugs. Computational simulation showed that actin cortex and microtubules are the major components targeted in resisting compression. This is a new numerical tool that explains the specific role of the cortex and overcomes the difficulty of isolating this component from other networks in vitro. This illustrates that a combination of cytoskeletal structures with their own properties is necessary for a complete description of cellular mechanics.

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KW - Finite element modeling

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KW - Microtubules

KW - AFM (atomic force microscopy)

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