Agents in Biology
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ticle distribution within capillaries. Furthermore, this model demonstrated how nanoparticle size can selectively target tumor tissue over
normal tissue. The authors showed that the polydispersity of nanoparticle populations is an important consideration in achieving optimal specificity and to avoid off-target effects. In the future, this model could be
used for informing new nanoparticle design and to predict general and
specific uptake properties under blood flow [71].
7.1.2 Tissue and Organ Models
Epithelial tissue and wound healing. Transforming growth factor (TGFβ1) is a member of the TGF-beta superfamily ligand-receptor network.
It 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-epithelialization it acts as proliferation inhibitor for keratinocytes. The majority of biological models
focus on certain aspects of TGF-β1 behavior and no one model provides
a comprehensive story of this regulatory factor’s action. Accordingly
the model’s aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-β1. In a
previous study, an agent-based model of keratinocyte colony formation
in 2D culture was developed. In this study, the model was extensively
developed into a 3D multiscale model of the human epidermis which is
comprised of three interacting and integrated layers:
• 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 behaviors.
• A COmplex PAthway SImulator (COPASI) model which simulates
the expression and signalling of TGF-β1 at the sub-cellular level.
• A mechanical layer embodied by a numerical physical solver responsible for resolving the forces exerted between cells at the multicellular level.
The integrated model was initially validated by using it to grow a piece
of virtual epidermis in 3D and comparing the in virtuo simulations of
keratinocyte behavior and of TGF-β1 signalling, with extensive research
describing the key regulatory protein. This research reinforced the idea
that computational modeling can be an effective additional tool to aid
understanding of complex systems. In the paper produced, the model
was used to explore the hypotheses on functions of TGF-β1 at the cellular and subcellular level on different keratinocyte populations during
epidermal wound healing [2].
Oviduct and sperm motility. The processes by which individual sperm
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