A checkpoint-oriented cell cycle simulation model

被引:22
作者
Bernard, David [1 ,2 ]
Mondesert, Odile [2 ]
Gomes, Aurelie [2 ]
Duthen, Yves [1 ,2 ]
Lobjois, Valerie [2 ]
Cussat-Blanc, Sylvain [1 ,2 ]
Ducommun, Bernard [2 ,3 ]
机构
[1] Univ Toulouse, CNRS, UT1, IRIT, Toulouse, France
[2] Univ Toulouse, CNRS, UT3, ITAV, Toulouse, France
[3] CHU Toulouse, Toulouse, France
关键词
Cell cycle; in silico simulation; agent-based modeling; synchronization; TUMOR-GROWTH; IN-VITRO; MATHEMATICAL-MODEL; AUTOMATON MODEL; POPULATIONS; DIVISION; CANCER; SYNCHRONIZATION; IDENTIFICATION;
D O I
10.1080/15384101.2019.1591125
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Modeling and in silico simulations are of major conceptual and applicative interest in studying the cell cycle and proliferation in eukaryotic cells. In this paper, we present a cell cycle checkpoint-oriented simulator that uses agent-based simulation modeling to reproduce the dynamics of a cancer cell population in exponential growth. Our in silico simulations were successfully validated by experimental in vitro supporting data obtained with HCT116 colon cancer cells. We demonstrated that this model can simulate cell confluence and the associated elongation of the G1 phase. Using nocodazole to synchronize cancer cells at mitosis, we confirmed the model predictivity and provided evidence of an additional and unexpected effect of nocodazole on the overall cell cycle progression. We anticipate that this cell cycle simulator will be a potential source of new insights and research perspectives.
引用
收藏
页码:795 / 808
页数:14
相关论文
共 52 条
[11]  
Creanor J, 1995, CELL CYCLE MAT METHO, P132
[12]  
Darzynkiewicz Z, 1993, CELL CYCLE PRACTICAL, P45
[13]   Coarse graining in simulated cell populations [J].
Drasdo, D .
ADVANCES IN COMPLEX SYSTEMS, 2005, 8 (2-3) :319-363
[14]   A single-cell-based model of tumor growth in vitro:: monolayers and spheroids [J].
Drasdo, D ;
Höhme, S .
PHYSICAL BIOLOGY, 2005, 2 (03) :133-147
[15]  
Drasdo D, 2018, NUMERICAL METHODS AD, P223, DOI DOI 10.1016/B978-0-12-811718-7.00012-5
[16]   Essential operating principles for tumor spheroid growth [J].
Engelberg, Jesse A. ;
Ropella, Glen E. P. ;
Hunt, C. Anthony .
BMC SYSTEMS BIOLOGY, 2008, 2
[17]   Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer [J].
Gatenby, R. A. ;
Smallbone, K. ;
Maini, P. K. ;
Rose, F. ;
Averill, J. ;
Nagle, R. B. ;
Worrall, L. ;
Gillies, R. J. .
BRITISH JOURNAL OF CANCER, 2007, 97 (05) :646-653
[18]   Cell Cycle Control by a Minimal Cdk Network [J].
Gerard, Claude ;
Tyson, John J. ;
Coudreuse, Damien ;
Novak, Bela .
PLOS COMPUTATIONAL BIOLOGY, 2015, 11 (02)
[19]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[20]  
HARTWELL LH, 1978, J CELL BIOL, V77, P627, DOI 10.1083/jcb.77.3.627