Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition." The study presented here provides a quantitative characterization of contact inhibition dynamics on tissuewide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size, and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition.EMT | growth regulation | mechanics | mitosis

We present a multiview selective-plane illumination microscope (MuVi-SPIM), comprising two detection and illumination objective lenses, that allows rapid in toto fluorescence imaging of biological specimens with subcellular resolution. The fixed geometrical arrangement of the imaging branches enables multiview data fusion in real time. The high speed of MuVi-SPIM allows faithful tracking of nuclei and cell shape changes, which we demonstrate through in toto imaging of the embryonic development of Drosophila melanogaster.

Significance Spatiotemporal coordination of cell growth underlies tissue development and disease. Mechanical feedback between cells has been proposed as a regulatory mechanism for growth control both in vivo and in cultured cells undergoing contact inhibition of proliferation. Evidence beyond theoretical and correlative observations falls short. In this study, we probe the impact of mechanical tissue perturbations on cell cycle progression by monitoring cell cycle dynamics of cells in tissues subject to acute changes in boundary conditions, as well as tissue stretching and compression. Taken together, we conclude that the ability of tissues to support cell cycle progression adapts to the available space through a memory-free control mechanism, which may coordinate proliferation patterns to maintain tissue homeostasis.

Point-like motile topological defects control the universal dynamics of diverse twodimensional active nematics ranging from shaken granular rods to cellular monolayers. A comparable understanding in higher dimensions has yet to emerge. We report the creation of three-dimensional active nematics by dispersing extensile microtubule bundles in a passive colloidal liquid crystal. Light-sheet microscopy reveals the millimeter-scale structure of active nematics with a single bundle resolution and the temporal evolution of the associated nematic director field. The dominant excitations of three-dimensional active nematics are extended charge-neutral disclination loops that undergo complex dynamics and recombination events. These studies introduce a distinct class of non-equilibrium systems whose turbulent-like dynamics arises from the interplay between internally generated active stresses, the chaotic flows and the topological structure of the constituent defects.