development of a three dimensional multiscale computational model of the human epidermis三维多尺度计算模型的发展人类的表皮.pdfVIP

Development of a Three Dimensional Multiscale Computational Model of the Human Epidermis 1 2 3 1 1 Salem Adra *, Tao Sun , Sheila MacNeil , Mike Holcombe , Rod Smallwood * 1 Department of Computer Science, University of Sheffield, Sheffield, United Kingdom, 2 Centre for Cell Engineering, University of Glasgow, Glasgow, United Kingdom, 3 Department of Engineering Materials, University of Sheffield, Sheffield, United Kingdom Abstract Transforming Growth Factor (TGF- b1) is a member of the TGF-beta superfamily ligand-receptor network. and plays a crucial role in tissue regeneration. The extensive in vitro and in vivo experimental literature describing its actions nevertheless describe an apparent paradox in that during re-epithelialisation it acts as proliferation inhibitor for keratinocytes. The majority of biological models focus on certain aspects of TGF-b1 behaviour and no one model provides a comprehensive story of this regulatory factor’s action. Accordingly our aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-b1. In our previous study, an agent-based model of keratinocyte colony formation in 2D culture was developed. In this study this model was extensively developed into a three dimensional multiscale model of the human epidermis which is comprised of three interacting and integrated layers: (1) an agent-based model which captures the biological rules governing the cells in the human epidermis at the cellular level and includes the rules for injury induced emergent behaviours, (2) a COmplex PAthway SImulator (COPASI) model which simulates the expression and signalling of TGF-b1 at the sub-cellular