Abstract

In our presentation, a new framework for modelling biological systems based on discrete particles. Collections of discrete particles are employed to represent cell components (e.g. cell membranes, cell cytoskeleton, cell nucleus) and extracellular matrix (e.g. collagen). Virtual interactions between particles can be used to represent many physical interaction types (e.g. cell-cell adhesion via cadherins, integrin basement membrane attachment, cytoskeletal mechanical properties). Particles may be given the capacity to change their properties and behaviours in response to changes in the cellular microenvironment (e.g., in response to cell-cell signalling or mechanical loadings). Each particle is in effect and ‘agent’, meaning that the agent can sense local environmental information and respond according to pre-determined or stochastic logical operators. After presenting this framework we show some initial examples demonstrating the capabilities of the modelling framework in two spatial dimensions Examples are given of: 1. Mechanical calibration of a single cell and nucleus data from a plate load test 2. Changes in a single cell shape with changing cell-basement membrane adhesion 3. Effect on epithelial layer of changing cell-cell (e.g. cadherin) and cell-basement membrane adhesion 4. Deformation of an epithelial sheet (comprising the stroma, collagen and mucus), including buckling and columnar-to-squamous transitions. These examples illustrate how the modeling framework allows enormous flexibility for representing different tissues, and we argue this offers a more intuitive approach than perhaps offered by a traditional continuum approaches. As such, we believe the discrete modelling framework will allow biologists and bioengineers to explore the behaviour of tissue systems in a computational laboratory.