Mechanistic Manipulation of Cytoskeletal Cortical Tension to Influence Cell Volume
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Date
2019-05-13
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Johns Hopkins University
Abstract
The regulation of cell volume in mammalian cells has long been a confounding topic of research. Identifying the various mechanisms that cells use to regulate their volume and morphology could allow us to recognize how these mechanisms become dysregulated. These dysregulations lead to uncontrolled growth, as is seen in cancerous cells. Previously, much of the work surrounding how cells regulate their behavior has focused on biochemical pathways. While the biochemistry within the microenvironment of the cell is not insignificant, the effects of physical phenomena, such as cortical tension, are often overlooked despite their importance. Measurement of these physical phenomena is very challenging to accomplish directly without disrupting the cell. Thus, biochemical regulators of these physical phenomena have gained notoriety. Two of these regulators are the Hippo pathway, most notably the components yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), and phosphorylated myosin light chain (pMLC). In this study, I use the fluorescence exclusion method to analyze how cell volume changes with respect to cell tension regulation with YAP/TAZ and pMLC activity. The dynamic changes of volume with cortical tension depletion suggest that the volume change is related to physical, not biochemical, phenomena. YAP/TAZ activity as a mechanosensor has a strong correlation with cell volume through its regulation of the G1/S phase transition. Decreased levels of pMLC lead to a decrease in cell volume and drastic morphology change within a period of two hours. This study reveals that the modulation of the cytoskeletal cortical tension on its own has the capability of drastically changing mammalian cell volume and morphology.
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Keywords
Cell Volume, Cortical Tension, Y-27632, Hippo, YAP/TAZ