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The ability of cells to maintain a constant level of cytoskeletal tension in response to external and internal disturbances is referred to as tensional homeostasis. It is essential for the normal physiological function of cells and tissues, and for protection against disease progression, including atherosclerosis and cancer. In previous studies, we defined tensional homeostasis as the ability of cells to maintain a consistent level of cytoskeletal tension with low temporal fluctuations. In those studies, we measured temporal fluctuations of cell-substrate traction forces in clusters of endothelial cells and of fibroblasts. We observed those temporal fluctuations to decrease with increasing cluster size in endothelial cells, but not in fibroblasts. We quantified temporal fluctuation, and thus homeostasis, through the coefficient of variation (CV) of the traction field; the lower the value of CV, the closer the cell is to the state of tensional homeostasis. This metric depends on correlation between individual traction forces. In this study, we analyzed the contribution of correlation between traction forces on traction field CV in clusters of endothelial cells and fibroblasts using experimental data that we had obtained previously. Results of our analysis showed that positive correlation between traction forces was detrimental to homeostasis, and that it was cell type-dependent.
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Tensional homeostasis at different length scales.
Tensional homeostasis is a phenomenon of fundamental importance in mechanobiology. It refers to the ability of organs, tissues, and cells to respond to external disturbances by maintaining a homeostatic (set point) level of mechanical stress (tension). It is well documented that breakdown in tensional homeostasis is the hallmark of progression of diseases, including cancer and atherosclerosis. In this review, we surveyed quantitative studies of tensional homeostasis with the goal of providing characterization of this phenomenon across a broad range of length scales, from the organ level to the subcellular level. We considered both static and dynamics approaches that have been used in studies of this phenomenon. Results that we found in the literature and that we obtained from our own investigations suggest that tensional homeostasis is an emergent phenomenon driven by collective rheostatic mechanisms associated with focal adhesions, and by a collective action of cells in multicellular forms, whose impact on tensional homeostasis is cell type-dependent and cell microenvironment-dependent. Additionally, the finding that cadherins, adhesion molecules that are important for formation of cell–cell junctions, promote tensional homeostasis even in single cells, demonstrates their relevance as a signaling moiety.
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- Award ID(s):
- 1910401
- PAR ID:
- 10222162
- Date Published:
- Journal Name:
- Soft matter
- Volume:
- 16
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 6946 - 6963
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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When adherent cells are subjected to uniaxial sinusoidal stretch at frequencies close to physiological, their body and their contractile stress fibers realign nearly perpendicularly to the stretch axis. A common explanation for this phenomenon is that stress fibers reorient along the direction where they are unaffected by the applied cyclic stretch and thus can maintain optimal (homeostatic) tensile force. The ability of cells to achieve tensional homeostasis in response to external disturbances is important for normal physiological functions of cells and tissues and it provides protection against diseases, including cancer and atherosclerosis. However, quantitative experimental data that support the idea that stretch-induced reorientation is associated with tensional homeostasis are lacking. We observed previously that in response to uniaxial cyclic stretch of 10% strain amplitudes, traction forces of single endothelial cells reorient in the direction perpendicular to the stretch axis. Here we carried out a secondary analysis of those data to investigate whether this reorientation of traction forces is associated with tensional homeostasis. Our analysis showed that stretch-induced reorientation of traction forces was accompanied by attenuation of temporal variability of the traction field to the level that was observed in the absence of stretch. These findings represent a quantitative experimental evidence that stretch-induced reorientation of the cell’s traction forces is associated with the cell’s tendency to achieve tensional homeostasis.more » « less
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Drs Humphrey and Cyron wrote a commentary regarding our review article entitled “Tensional homeostasis at different length scales” that was published in Soft Matter , 2020, 16 , 6946–6963. These authors brought up some valid concerns to which we would like to respond. Their first concern is related to our remark regarding equations that we used to describe homeostasis in blood vessels, where we stated that those equations were limited only to linearly elastic materials. We were wrong, and we agree with the authors that these equations hold for all cylindrical vessels regardless of their material properties. Their second concern is related to tensional homeostasis at the subcellular level. Drs Humphrey and Cyron disagree with our substantiated claim that tensional homeostasis breaks down at the level of focal adhesions (FAs) of a living cell. In our reply, we provided several pieces of evidence that demonstrate that tensional homeostasis depends upon FA size, FA maturity and FA force dynamics and thus, tensional homeostasis cannot hold in all FAs across a cell. In summary, we are grateful for the opportunity to reply to the commentary of Drs Humphrey and Cyron. Moreover, we are excited that this topic has become an important focus in the biomechanics and mechanobiology communities, and we feel strongly that critical feedback is necessary to move this field forward.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0sm00763c
