Singh Jaykrishna, Hussain Fazle, Decuzzi Paolo
a Department of Translational Imaging , The Methodist Hospital Research Institute (TMHRI) , Houston , TX , USA.
Comput Methods Biomech Biomed Engin. 2015;18(3):282-92. doi: 10.1080/10255842.2013.792917. Epub 2013 May 8.
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 (JCC) and cell-matrix (JMC) 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 JCC) and high heterotypic adhesion (low JMC) favours the fragmentation of the original cluster into multiple, smaller cell clusters (metastasis). Conversely, cellular systems exhibiting high-homotypic affinity (low JCC) preserve their original configuration, avoiding fragmentation (organogenesis). For intermediate values of JCC and JMC (i.e. JCC/JMC ∼ 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.
细胞间和细胞与基质的黏附对于众多生理过程至关重要，包括血管生成、肿瘤发生、转移扩散和伤口愈合。我们使用细胞Potts模型通过计算预测三维基质中细胞的组织方式。调节细胞间（JCC）和细胞与基质（JMC）黏附相互作用的能量势会系统地变化，以代表不同的、与生物学相关的黏附条件。还研究了趋化诱导的细胞迁移。从一群细胞开始，仅相对细胞黏附的变化就会导致不同的细胞模式，如转移性肿瘤的扩散和血管生成。低细胞间黏附（高JCC）和高异型黏附（低JMC）的组合有利于原始细胞簇分裂成多个较小的细胞簇（转移）。相反，表现出高同型亲和力（低JCC）的细胞系统保持其原始构型，避免分裂（器官发生）。对于JCC和JMC的中间值（即JCC/JMC ∼ 1），会形成管状和波纹状结构。只有在细胞接触时激活接触抑制趋化作用的系统中，才能组装出完全发育的血管树。此外，趋化因子的分泌、扩散和隔离速率、细胞可变形性和运动性不会显著影响这些趋势。该计算模型的进一步发展将预测通过直接改变细胞黏附来调节患病微环境的治疗干预效果。
