@article{Subcellular:5708,
      recid = {5708},
      author = {Chmiel, Theresa Ann},
      title = {Decoding Epithelial Forces: How Cellular Forces Propagate  and Are Regulated from Subcellular to Tissue Scales},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-03},
      pages = {149},
      abstract = {	Our understanding of the mechanics of multi-scale  cellular biology continues to improve as we study the  complex balance of forces found in tissues from the  subcellular to the tissue scale. Determining the links  between how subcellular protein activity regulates cell  shape and volume and how those changes to shape and volume  affect tissue architecture as a whole is vital to our  understanding of cellular processes from embryo development  and organization to the uncontrolled growth of cancerous  masses.  Here, we add to this body of work by examining how  perturbations to subcellular forces, both internal and  external, affect individual cell shape, motility, and  overall homeostasis as well as how these forces propagate  and affect tissue-scale change. Using model epithelial (and  in one case endothelial) tissue, we examine various  internal and external perturbations to cell force. This  includes internal modifications to junctional tension from  local ROCK inhibition and activation as well as modifying  the presence and localization of the force sensitive LIM  domain protein FHL2. It also includes the application of  external forces through processes such as the addition of  hyperosmotic media to create osmotic pressure changes,  applying a DC electric field to induce transient calcium  spikes implicated in electrotaxis, and applying shear  stress through disturbances to apical fluid flow.  Ultimately, we find that cell shape, volume, and cell  motility is controlled through various underlying  biophysical mechanisms from active membrane tension to  cell-cell adhesion to local ion concentration. We also show  that cell shape, volume, and motility regulation in  response to force perturbations affect cells differently in  small colonies compared to mature epithelial tissue,  underscoring the importance of collective behavior in the  regulation of tissue-scale dynamic processes. },
      url = {http://knowledge.uchicago.edu/record/5708},
      doi = {https://doi.org/10.6082/uchicago.5708},
}