title: Vertical uniformity of cells and nuclei in epithelial monolayers.
abstract: Morphological variability in cytoskeletal organization, organelle position and cell boundaries is a common feature of cultured cells. Remarkable uniformity and reproducibility in structure can be accomplished by providing cells with defined geometric cues. Cells in tissues can also self-organize in the absence of directing extracellular cues; however the mechanical principles for such self-organization are not understood. We report that unlike horizontal shapes, the vertical shapes of the cell and nucleus in the z-dimension are uniform in cells in cultured monolayers compared to isolated cells. Apical surfaces of cells and their nuclei in monolayers were flat and heights were uniform. In contrast, isolated cells, or cells with disrupted cell-cell adhesions had nuclei with curved apical surfaces and variable heights. Isolated cells cultured within micron-sized square wells displayed flat cell and nuclear shapes similar to cells in monolayers. Local disruption of nuclear-cytoskeletal linkages resulted in spatial variation in vertical uniformity. These results suggest that competition between cell-cell pulling forces that expand and shorten the vertical cell cross-section, thereby widening and flattening the nucleus, and the resistance of the nucleus to further flattening results in uniform cell and nuclear cross-sections. Our results reveal the mechanical principles of self-organized vertical uniformity in cell monolayers.
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville FL 32611 USA.
authors.forename: Srujana
authors.initials: S
authors.lastname: Neelam
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611.
authors.forename: Peter Robert
authors.initials: PR
authors.lastname: Hayes
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Dickinson
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL 32611.
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
mesh_terms: D001940:Breast / Q000166:cytology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D053144:Cell Nucleus Shape; D002469:Cell Separation; D048430:Cell Shape; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans
chemical_list: D015820:Cadherins