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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.