期刊
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING
卷 18, 期 3, 页码 282-292出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10255842.2013.792917
关键词
cellular potts model; chemotaxis; pattern formation; cell-cell adhesion; cell-matrix adhesion; cellular organisation
资金
- Cancer Prevention Research Institute of Texas through CPRIT [RP110262]
- National Institutes of Health (USA) (NIH) [U54CA143837, U54CA151668]
Cell-cell and cell-matrix adhesions are fundamental to numerous physiological processes, including angiogenesis, tumourigenesis, metastatic spreading and wound healing. We use cellular potts model to computationally predict the organisation of cells within a 3D matrix. The energy potentials regulating cell-cell (J(CC)) and cell-matrix (J(MC)) adhesive interactions are systematically varied to represent different, biologically relevant adhesive conditions. Chemotactically induced cell migration is also addressed. Starting from a cluster of cells, variations in relative cell adhesion alone lead to different cellular patterns such as spreading of metastatic tumours and angiogenesis. The combination of low cell-cell adhesion (high J(CC)) and high heterotypic adhesion (low J(MC)) favours the fragmentation of the original cluster into multiple, smaller cell clusters (metastasis). Conversely, cellular systems exhibiting high-homotypic affinity (low J(CC)) preserve their original configuration, avoiding fragmentation (organogenesis). For intermediate values of J(CC) and J(MC) (i.e. J(CC)/J(MC) similar to 1), tubular and corrugated structures form. Fully developed vascular trees are assembled only in systems in which contact-inhibited chemotaxis is activated upon cell contact. Also, the rate of secretion, diffusion and sequestration of chemotactic factors, cell deformability and motility do not significantly affect these trends. Further developments of this computational model will predict the efficacy of therapeutic interventions to modulate the diseased microenvironment by directly altering cell cohesion.
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