Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis

Abstract

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast's capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex-membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.

A multi-structural finite element model to simulate atomic force microscopy nanoindentation of single cells

“…1A in white and yellow). Their organisation and dimensions were chosen from the confocal imaging information: the basal actin bundles roughly followed the morphology of the cell and were tied to the cytoplasm at nodes regarded as focal adhesions; the apical actin bundles were designed to join the nucleus and the cytoplasm in a parallel fashion [15,18] and were therefore tied to the nucleus on one end. A cross-section of all truss elements was chosen equal to 0.2 µm 2 .…”

“…The actin cortex ( Fig. 1A in green) was modelled as a thin shell homogeneously covering the cell surface [1,18]. A thickness of 0.2 µm was chosen [1,8,9].…”

“…A thickness of 0.2 µm was chosen [1,8,9]. The cell membrane was not included in the model as it was considered negligible in terms of mechanical deformation resistance, as it is much softer than the actin cortex [1,18].…”

“…Materials [18] and element types for each subcellular component are summarised in Table 1. Homogeneous, isotropic and elastic material properties were assumed.…”

“…The model comprised the nucleus, the cytoplasm and the actin cytoskeleton. The latter was modelled as actin bundles resisting tensional forces [1,11,15,18] and actin cortex responding to compression [1,18]. The use of confocal stack images of a representative cell of a bone cell line allowed for faithful representation of the cell shape and of the arrangement of the actin bundles.…”