Jeremiah J Zartman | Search bioRxiv

bioRxiv2016

Robust cell tracking in epithelial tissues through identification of maximum common subgraphs

Tracking of cells in live-imaging microscopy videos of epithelial sheets is a powerful tool for investigating fundamental processes in embryonic development. Characterising cell growth, proliferation, intercalation and apoptosis in epithelia helps us to understand how morphogenetic processes such as tissue invagination and extension are locally regulated and controlled. Accurate cell tracking requires correctly resolving cells entering or leaving the field of view between frames, cell neighbour exchanges, cell removals and cell divisions. However, current tracking methods for epithelial sheets are not robust to large morphogenetic deformations and require significant manual interventions. Here, we present a novel algorithm for epithelial cell tracking, exploiting the graph-theoretic concept of a maximum common subgraph to track cells between frames of a video. Our algorithm does not require the adjustment of tissue-specific parameters, and scales in sub-quadratic time with tissue size. It does not rely on precise positional information, permitting large cell movements between frames and enabling tracking in datasets acquired at low temporal resolution due to experimental constraints such as photoxicity. To demonstrate the method, we perform tracking on the Drosophila embryonic epidermis and compare cell-cell rearrangements to previous studies in other tissues. Our implementation is open source and generally applicable to epithelial tissues.

Bioengineering↗

bioRxiv2016

Predictive multi-scale computational environment for studying epithelial dynamics

Mitotic rounding (MR) during cell division is critical for the robust segregation of chromosomes into daughter cells and is frequently perturbed in cancerous cells. MR has been studied extensively in individual cultured cells, but the physical mechanisms regulating MR in intact tissues are still poorly understood. A cell undergoes mitotic rounding by simultaneously reducing adhesion with its neighbors, increasing actomyosin contraction around the cortex, and increasing the osmotic pressure of the cytoplasm. Whether these changes are purely additive, synergistic or impact separate aspects of MR is not clear. Specific modulation of these processes in dividing cells within a tissue is experimentally challenging, because of off-target effects and the difficulty of targeting only dividing cells. In this study, we analyze MR in epithelial cells by using a newly developed multi-scale, cell-based computational model that is calibrated using experimental observations from a model system of epithelial tissue growth, the Drosophila wing imaginal disc. The model simulations predict that increase in apical surface area of mitotic cells is solely driven by increasing cytoplasmic pressure. MR however is not achieved within biological constraints unless all three properties (cell-cell adhesion, cortical stiffness and pressure) are simultaneously regulated by the cell. The new multi-scale model is computationally implemented using a parallelization algorithm on a cluster of graphic processing units (GPUs) to make simulations of tissues with a large number of cells feasible. The model is extensible to investigate a wide range of cellular phenomena at the tissue scale.\n\nAuthor SummaryMitotic rounding (MR) during cell division is critical for the robust segregation of chromosomes into daughter cells and is frequently perturbed in cancerous cells. MR has been studied extensively in individual cultured cells, but the physical mechanisms regulating MR in intact tissues are still poorly understood. The newly developed computational model Epi-scale enables one to produce new hypotheses about the underlying biophysical mechanisms governing MR of epithelial cells within the developing tissue micro-environment. In particular, our simulations results predict that robust mitotic rounding requires co-current changes in cell-cell adhesion, cortical stiffness and cytoplasmic pressure, and explains how regulation of each property impacts the shapes of dividing cells in tissues.

Biophysics↗