Cellular mechanosensitivity to substrate stiffness decreases with increasing dissimilarity to cell stiffness

Davies

Franz

2019

Preprint

Self Cite

Existing in silico models for single cells feature limited representations of cytoskeletal structures that present inhomogeneities in the cytoplasm and contribute substantially to the mechanical behaviour of the cell. Considering these microstructural inhomogeneities is expected to provide more realistic predictions of cellular and subcellular mechanics. Here, we propose a micromechanical hierarchical approach to capture the contribution of actin stress fibres to the mechanical behaviour of a single cell when exposed to substrate stretch.For a cell-specific geometry of a fibroblast with membrane, cytoplasm and nucleus obtained from confocal micrographs, the Mori-Tanaka homogenization method was employed to account for cytoplasmic inhomogeneities and constitutive contribution of actin stress fibres. The homogenization was implemented in finite element models of the fibroblast attached to a planar substrate with 124 focal adhesions. With these models, the strains in cell membrane, cytoplasm and nucleus due to uniaxial substrate stretch of 1.1 were assessed for different stress fibre volume fractions in the cytoplasm of up to 20% and different elastic modulus of the substrate. A considerable decrease of the peak strain with increasing stress fibre content was observed in cytoplasm and nucleus but not the cell membrane, whereas peak strain increased in cytoplasm, nucleus and membrane for increasing elastic modulus of the substrate. With the potential for extension, the developed method and models can contribute to more realistic in silico models of cellular mechanics.

Section: Geometrical Modellingmentioning

confidence: 99%

Section: (B)mentioning

confidence: 99%

Section: Nucleusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

In silico stress fibre content affects peak strain in cytoplasm and nucleus but not in the membrane for uniaxial substrate stretch

Davies

Franz

2019

Preprint

Self Cite

Cell focal adhesion clustering leads to decreased and homogenized basal strains

Kohn

Numer Methods Biomed Eng

Sack

et al. 2019

Self Cite

The subendothelial matrix of the artery is a complex mechanical environment where endothelial cells respond to and affect changes upon the underlying substrate. Our recent work has demonstrated that endothelial cell strain heterogeneity increases on a more heterogeneous underlying subendothelial matrix, and these cells display increased focal adhesion presence on stiffer substrate areas. However, the impact of these grouped focal adhesions on endothelial cell strains has not been explored. Here, we use finite element modeling to investigate the effects of micro-scale stiffness heterogeneities and focal adhesion location and stiffness on endothelial cell strains. Shear stress applied to the apical cell layer demonstrated a minimal effect on cell strain values while substrate stretch had a greater effect on cell strain in the cell-substrate model. The addition of focal adhesions into the computational model (cell-FA-substrate model) predicted a decrease and homogenization of the cell strains. For simulations including focal adhesions, stiffer and more distributed adhesions caused increased and more heterogeneous endothelial cell strains. Overall, our data indicate that cells may group focal adhesions to minimize and homogenize their basal strains.

In silico stress fibre content affects peak strain in cytoplasm and nucleus but not in the membrane for uniaxial substrate stretch

Davies

Franz

2021

Med Biol Eng Comput

Existing in silico models for single cell mechanics feature limited representations of cytoskeletal structures that contribute substantially to the mechanics of a cell. We propose a micromechanical hierarchical approach to capture the mechanical contribution of actin stress fibres. For a cell-specific fibroblast geometry with membrane, cytoplasm and nucleus, the Mori-Tanaka homogenization method was employed to describe cytoplasmic inhomogeneities and constitutive contribution of actin stress fibres. The homogenization was implemented in a finite element model of the fibroblast attached to a substrate through focal adhesions. Strain in cell membrane, cytoplasm and nucleus due to uniaxial substrate stretch was assessed for different stress fibre volume fractions and different elastic modulus of the substrate. A considerable decrease of the peak strain with increasing stress fibre content was observed in cytoplasm and nucleus but not the membrane, whereas the peak strain in cytoplasm, nucleus and membrane increased for increasing elastic modulus of the substrate.