DCIS Simulation -- Fluid artisan "wetting" behaviour from aerial arrangement of adherence forces

!±8± DCIS Simulation -- Fluid artisan "wetting" behaviour from aerial arrangement of adherence forces

Agent-based simulation of ductal carcinoma in situ (DCIS), a type of breast cancer that is constrained to growth in the breast duct lumen by a basement membrane. Shown here: a simulation of 30 days' growth in a 1mm length of duct. The mechanical and population dynamic parameters have been calibrated to patient-specific immunohistochemistry and other histologic measurements. In this simulation, the ratio of the strength of cell-basement membrane adhesion to cell-cell adhesion is 100:1. This leads to unrealistic fluid mechanic "wetting" behaviour, where cells cannot easily detach from the duct wall and slide along the (frictionless) wall. Higher oxygen levels along the wall act as a nonlinear feedback by promoting more rapid proliferation in these cells, accelerating the process. Instead, cell-cell and cell-wall adhesion should be of more comparable strength. Dark circles: cell nuclei Green cells: proliferating cells (Ki-67 positive; S, G2, M, or G1) Red cells: apoptosis cells (cleaved Caspase-3 positive) Pale blue cells: quiescent cells (G0) Dark grey cells: necrotic cells prior to lysis Debris in centre of duct: necrotic cellular debris Red dots in centre of duct: clinically-detectable microcalcifications Method: Agent-based, lattice-free model. Cell velocities determined by balance of adhesive and repulsive forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes. Source: Macklin et al. 2011 in review. See ...

DCIS Simulation -- Fluid artisan "wetting" behaviour from aerial arrangement of adherence forces

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