Cell mechanosensitivity: mechanical properties and interaction with gravitational field

I V Ogneva, I V Ogneva

Abstract

This paper addressed the possible mechanisms of primary reception of a mechanical stimulus by different cells. Data concerning the stiffness of muscle and nonmuscle cells as measured by atomic force microscopy are provided. The changes in the mechanical properties of cells that occur under changed external mechanical tension are presented, and the initial stages of mechanical signal transduction are considered. The possible mechanism of perception of different external mechanical signals by cells is suggested.

Figures

Figure 1
Figure 1
General mechanotransduction schemas. Changes in the external mechanical load cause a change in the internal mechanical tension of the cell and its deformation. Deformations can occur in the ion channels causing changes in their permeability for different ions, for example for calcium, which is a secondary messenger and can activate some signalling pathways. Moreover, deformations can also occur in the cytoskeleton, both in the sarcomere (for muscle cells) and cortical cytoskeleton, causing the release of different signalling molecules and activation of downstream signalling pathways. The final result will be a change in the cell's mechanical properties, its functional activity, and formation of adaptive patterns in gene expression.
Figure 2
Figure 2
Hypothetical mechanism for earlier cellular responses to changes in mechanical conditions. The principal difference between stretch and compression is characterized by the dissociation of different molecules from the cortical cytoskeleton, for example, alpha-actinin-1 at stretching and alpha-actinin-4 at compression. Under cell stretch, there are cortical cytoskeleton deformations and subsequent shifts in actin filaments relative to each other in the stress fibres. This increases the probability of dissociation of the proteins that connect actin filaments, for example, alpha-actinin-1. Under cell compression, this happens predominantly via membrane deformation so that the conformation of the alpha-actinin-4 binding sites (e.g., due to cholesterol raft convergence) can change. This will lead to a release of proteins which connect with the membrane, for example, alpha-actinin-4. The release of alpha-actinin-4 causes the activation of the expression of the alpha-actinin-1 gene and repression of own expression. This occurs similarly for alpha-actinin-1. The release of different proteins causes activation of different pathways and formation of the response to the increase or decrease in mechanical load. The proposed mechanism is only hypothetical and therefore needs to be checked experimentally.
Figure 3
Figure 3
Hypothetical mechanism for the development of adaptive responses of skeletal muscle fibres and cardiomyocytes to the change in mechanical conditions. An increase in the external mechanical load on the cardiomyocytes in early stages of antiorthostatic disuse in rats should naturally cause an increase in the cell's ability to resist it, that is, an increase in cell stiffness and development of the cytoskeleton, in addition to an intensification of the cell respiration. Decrease of the load on the rat skeletal muscle fibres during antiorthostatic disuse does not require the development of the cortical cytoskeleton, and as a result the cell's stiffness should decrease. Hypothetical links are shown by dashed arrowheads and contours. −/+: decrease/increase in protein content, from the left/to right—for load/disuse.

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Source: PubMed

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