title: Discrete Element Framework for Modelling Extracellular Matrix, Deformable Cells and Subcellular Components.
abstract: This paper presents a framework for modelling biological tissues based on discrete particles. Cell components (e.g. cell membranes, cell cytoskeleton, cell nucleus) and extracellular matrix (e.g. collagen) are represented using collections of particles. Simple particle to particle interaction laws are used to simulate and control complex 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 an 'agent', meaning that the agent can sense local environmental information and respond according to pre-determined or stochastic events. The behaviour of the proposed framework is exemplified through several biological problems of ongoing interest. These examples illustrate how the modelling framework allows enormous flexibility for representing the mechanical behaviour of different tissues, and we argue this is a more intuitive approach than perhaps offered by traditional continuum methods. Because of this flexibility, we believe the discrete modelling framework provides an avenue for biologists and bioengineers to explore the behaviour of tissue systems in a computational laboratory.
authors.affiliation: School of Engineering and Information Technology, Murdoch University, Perth, Australia.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Gardiner
authors.affiliation: Engineering Computational Biology, School of Computer Science and Software Engineering, The University of Western Australia, Perth, Australia.
authors.forename: Kelvin K L
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Intelligent Systems for Medicine Laboratory, School of Mechanical and Chemical Engineering, The University of Western Australia, Perth, Australia.
authors.forename: Grand R
authors.initials: GR
authors.lastname: Joldes
authors.affiliation: Engineering Computational Biology, School of Computer Science and Software Engineering, The University of Western Australia, Perth, Australia.
authors.forename: Addison J
authors.initials: AJ
authors.lastname: Rich
authors.affiliation: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Chin Wee
authors.initials: CW
authors.lastname: Tan
authors.affiliation: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
authors.affiliation: Engineering Computational Biology, School of Computer Science and Software Engineering, The University of Western Australia, Perth, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D000818:Animals; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D013347:Subcellular Fractions / Q000502:physiology*