Physiological tissue exists in a state of tension. Maintenance of this tension at a set level, a process termed tensional homeostasis, is imperative to the preservation of healthy cells and tissues, and multiple diseases such as cancer and atherosclerosis have been linked to the loss of the ability to maintain it. Despite this, very little is known about how this tension is established and maintained at the cellular level. Early reports on tensional homeostasis, which observed large cohorts of cells, hypothesized that constant tension levels exist at all length scales, including the cellular and subcellular length scales. Therefore, the main goal of this thesis was to begin to understand tensional homeostasis at the cellular level.
In this thesis, we explore the impacts of both cell properties and environmental factors on the traction force dynamics of single cells and clusters of cells to try to understand how they establish and maintain tensional homeostasis. We observed that multicellularity is necessary for tensional homeostasis in endothelial cells, but that this phenomenon is cell type specific. Cell types like smooth muscle and fibroblasts maintain steady force at the single cell level. We explored the differences that might drive this difference and found that the cell adhesion protein cadherin is essential to tensional homeostasis and that inflammatory signaling can lead to its loss. We also work towards the creation of a tool that will allow us to better recapitulate in vivo conditions, which will allow us to study tensional homeostasis at the single cell level in the physiological context of cyclic stretch.
This work suggests that tensional homeostasis is a complex process that is influenced by both internal and environmental factors. Some of these factors, like E-cadherin, which were previously known to affect mechanobiology may be more complex than previously realized. Finally, this thesis makes it clear that to fully understand how cells establish the homeostasis seen at the tissue level, we must look at traction dynamics rather than just a single snapshot in time. Studying tensional homeostasis in dynamic states may be essential to understanding processes such as wound healing, development, and disease progression.
|23 October 2018
|Smith, Michael L.
|Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/
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