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词条 Cell-based models
释义

  1. Model types

      Off-lattice    Vertex  

  2. Applications

  3. Simulation frameworks

  4. References

{{Orphan|date=August 2017}}Cell-based models are mathematical models that represent biological cells as a discrete entities. They are used in the field of computational biology for simulating the biomechanics of multicellular structures such as tissues. Their main advantage is the easy integration of cell level processes such as cell division, intracellular processes and single-cell variability within a cell population.[1]

Model types

Cell-based models can be divided into on- and off-lattice models. On-lattice models such as cellular automata or cellular potts restrict the spatial arrangement of the cells to a fixed grid. The mechanical interactions are then carried out according to literature-based rules (cellular automata)[2] or by minimizing the total energy of the system (cellular potts),[3] resulting in cells being displaced from one grid point to another.

Off-lattice

Off-lattice models allow for continuous movement of cells in space and evolve the system in time according to force laws governing the mechanical interactions between the individual cells. Examples of off-lattice models are center-based models, vertex-based models, models

based on the immersed boundary method[4] and the subcellular element

method.[5] They differ mainly in the level of detail with which they represent the

cell shape. As a consequence they vary in their ability to capture different biological mechanisms, the effort needed to extend them from two- to three-dimensional models and also in their computational cost.[6]

The simplest off-lattice model, the center-based model, depicts cells as spheres and models their mechanical interactions using pairwise potentials.[7][8] It is easily extended to a large number of cells in both 2D and 3D.[9]

Vertex

Vertex-based models track the cell membrane as a set of polygonal points and update the position of each vertex according to tensions in the cell membrane resulting from cell-cell adhesion forces and cell elasticity.[10] They are more difficult to implement and also more costly to run.

As cells move past one another during a simulation, regular updates of the polygonal edge connections are necessary.[11]

Applications

Since they account for individual behavior at the cell level such as cell proliferation, cell migration or apoptosis, cell-based models are a useful tool to study the influence of these behaviors on how tissues are organised in time and space.[1]

Due in part to the increase in computational power, they have arisen as an alternative to continuum mechanics models[12] which treat tissues as viscoelastic materials by averaging over single cells.

Cell-based mechanics models are often coupled to models describing intracellular dynamics, such as an ODE representation of a relevant gene regulatory network. It is also common to connect them to a PDE describing the diffusion of a chemical signaling molecule through the extracellular matrix, in order to account for cell-cell communication. As such, cell-based models have been used to study processes ranging from embryogenesis[13] over epithelial morphogenesis[14] to tumour growth[15] and intestinal crypt dynamics[16]

Simulation frameworks

There exist several software packages implementing cell-based models, e.g.

  • Chaste[17][18]
  • CompuCell3D[19]
  • CellSys[20]
  • Morpheus[21]
  • VirtualLeaf[22]
  • LBIBCell[23]
  • MecaGen[24]

References

1. ^1 {{cite journal | vauthors = Van Liedekerke P, Palm MM , Jagiella N, Drasdo D | title=Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results|journal=Computational Particle Mechanics|date=1 December 2015|volume=2|issue=4|pages=401–444|doi=10.1007/s40571-015-0082-3 }}
2. ^{{cite journal | vauthors = Peirce SM, Van Gieson EJ, Skalak TC | title = Multicellular simulation predicts microvascular patterning and in silico tissue assembly | journal = FASEB Journal | volume = 18 | issue = 6 | pages = 731–3 | date = April 2004 | pmid = 14766791 | doi = 10.1096/fj.03-0933fje | url = http://www.fasebj.org/content/18/6/731.short }}
3. ^{{cite journal | vauthors = Graner F, Glazier JA | title = Simulation of biological cell sorting using a two-dimensional extended Potts model | journal = Physical Review Letters | volume = 69 | issue = 13 | pages = 2013–2016 | date = September 1992 | pmid = 10046374 | doi = 10.1103/PhysRevLett.69.2013 }}
4. ^{{cite journal | vauthors = Rejniak KA | title = An immersed boundary framework for modelling the growth of individual cells: an application to the early tumour development | journal = Journal of Theoretical Biology | volume = 247 | issue = 1 | pages = 186–204 | date = July 2007 | pmid = 17416390 | doi = 10.1016/j.jtbi.2007.02.019 }}
5. ^{{cite book | vauthors = Newman TJ | title = Modeling multicellular systems using subcellular elements | journal = Mathematical Biosciences and Engineering | volume = 2 | issue = 3 | pages = 613–24 | date = July 2005 | pmid = 20369943 | doi = 10.1007/978-3-7643-8123-3_10 | series = Mathematics and Biosciences in Interaction | isbn = 978-3-7643-8101-1 }}
6. ^{{cite journal | vauthors = Osborne JM, Fletcher AG, Pitt-Francis JM, Maini PK, Gavaghan DJ | title = Comparing individual-based approaches to modelling the self-organization of multicellular tissues | journal = PLoS Computational Biology | volume = 13 | issue = 2 | pages = e1005387 | date = February 2017 | pmid = 28192427 | pmc = 5330541 | doi = 10.1371/journal.pcbi.1005387 }}
7. ^{{cite journal | vauthors = Meineke FA, Potten CS, Loeffler M | title = Cell migration and organization in the intestinal crypt using a lattice-free model | journal = Cell Proliferation | volume = 34 | issue = 4 | pages = 253–66 | date = August 2001 | pmid = 11529883 | doi = 10.1046/j.0960-7722.2001.00216.x }}
8. ^{{cite journal | vauthors = Drasdo D, Höhme S | title = A single-cell-based model of tumor growth in vitro: monolayers and spheroids | journal = Physical Biology | volume = 2 | issue = 3 | pages = 133–47 | date = July 2005 | pmid = 16224119 | doi = 10.1088/1478-3975/2/3/001 }}
9. ^{{cite journal | vauthors = Galle J, Aust G, Schaller G, Beyer T, Drasdo D | title = Individual cell-based models of the spatial-temporal organization of multicellular systems--achievements and limitations | journal = Cytometry. Part A | volume = 69 | issue = 7 | pages = 704–10 | date = July 2006 | pmid = 16807896 | doi = 10.1002/cyto.a.20287 }}
10. ^{{cite journal | vauthors = Fletcher AG, Osterfield M, Baker RE, Shvartsman SY | title = Vertex models of epithelial morphogenesis | journal = Biophysical Journal | volume = 106 | issue = 11 | pages = 2291–304 | date = June 2014 | pmid = 24896108 | pmc = 4052277 | doi = 10.1016/j.bpj.2013.11.4498 }}
11. ^{{cite journal | vauthors = Fletcher AG, Osborne JM, Maini PK, Gavaghan DJ | title = Implementing vertex dynamics models of cell populations in biology within a consistent computational framework | journal = Progress in Biophysics and Molecular Biology | volume = 113 | issue = 2 | pages = 299–326 | date = November 2013 | pmid = 24120733 | doi = 10.1016/j.pbiomolbio.2013.09.003 | url = http://www.sciencedirect.com/science/article/pii/S0079610713000989 }}
12. ^{{cite journal | vauthors = Rodriguez EK, Hoger A, McCulloch AD | title = Stress-dependent finite growth in soft elastic tissues | journal = Journal of Biomechanics | volume = 27 | issue = 4 | pages = 455–67 | date = April 1994 | pmid = 8188726 | doi = 10.1016/0021-9290(94)90021-3 }}
13. ^{{cite journal | vauthors = Tosenberger A, Gonze D, Bessonnard S, Cohen-Tannoudji M, Chazaud C, Dupont G | title = A multiscale model of early cell lineage specification including cell division | journal = NPJ Systems Biology and Applications | volume = 3 | issue = 1 | pages = 16 | date = 9 June 2017 | pmid = 28649443 | pmc = 5466652 | doi = 10.1038/s41540-017-0017-0 | url = https://www.nature.com/articles/s41540-017-0017-0 }}
14. ^{{cite journal | vauthors = Fletcher AG, Cooper F, Baker RE | title = Mechanocellular models of epithelial morphogenesis | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 372 | issue = 1720 | pages = 20150519 | date = May 2017 | pmid = 28348253 | pmc = 5379025 | doi = 10.1098/rstb.2015.0519 | url = http://rstb.royalsocietypublishing.org/content/372/1720/20150519 }}
15. ^{{cite book |last1=Drasdo|first1=Dirk |last2=Dormann |first2=Sabine |last3=Hoehme|first3=Stefan|last4=Deutsch|first4=Andreas | name-list-format = vanc |title=Cell-Based Models of Avascular Tumor Growth|journal=Function and Regulation of Cellular Systems|date=2004|pages=367–378|doi=10.1007/978-3-0348-7895-1_37|isbn=978-3-0348-9614-6 }}
16. ^{{cite journal | vauthors = De Matteis G, Graudenzi A, Antoniotti M | title = A review of spatial computational models for multi-cellular systems, with regard to intestinal crypts and colorectal cancer development | journal = Journal of Mathematical Biology | volume = 66 | issue = 7 | pages = 1409–62 | date = June 2013 | pmid = 22565629 | doi = 10.1007/s00285-012-0539-4 }}
17. ^{{cite journal | vauthors = Pitt-Francis J, Bernabeu MO, Cooper J, Garny A, Momtahan L, Osborne J, Pathmanathan P, Rodriguez B, Whiteley JP, Gavaghan DJ | title = Chaste: using agile programming techniques to develop computational biology software | journal = Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and Engineering Sciences | volume = 366 | issue = 1878 | pages = 3111–36 | date = September 2008 | pmid = 18565813 | doi = 10.1016/j.cpc.2009.07.019 | author16-link = Sarah L. Waters | url = http://eprints.maths.ox.ac.uk/846 }}
18. ^{{cite journal | vauthors = Mirams GR, Arthurs CJ, Bernabeu MO, Bordas R, Cooper J, Corrias A, Davit Y, Dunn SJ, Fletcher AG, Harvey DG, Marsh ME, Osborne JM, Pathmanathan P, Pitt-Francis J, Southern J, Zemzemi N, Gavaghan DJ | title = Chaste: an open source C++ library for computational physiology and biology | journal = PLoS Computational Biology | volume = 9 | issue = 3 | pages = e1002970 | date = 14 March 2013 | pmid = 23516352 | pmc = 3597547 | doi = 10.1371/journal.pcbi.1002970 }}
19. ^{{cite book | vauthors = Swat MH, Thomas GL, Belmonte JM, Shirinifard A, Hmeljak D, Glazier JA | title = Multi-scale modeling of tissues using CompuCell3D | journal = Methods in Cell Biology | volume = 110 | pages = 325–66 | date = 1 January 2012 | pmid = 22482955 | doi = 10.1016/B978-0-12-388403-9.00013-8 | pmc = 3612985 | isbn = 9780123884039 }}
20. ^{{cite journal | vauthors = Hoehme S, Drasdo D | title = A cell-based simulation software for multi-cellular systems | journal = Bioinformatics | volume = 26 | issue = 20 | pages = 2641–2 | date = October 2010 | pmid = 20709692 | pmc = 2951083 | doi = 10.1093/bioinformatics/btq437 }}
21. ^{{cite journal | vauthors = Starruß J, de Back W, Brusch L, Deutsch A | title = Morpheus: a user-friendly modeling environment for multiscale and multicellular systems biology | journal = Bioinformatics | volume = 30 | issue = 9 | pages = 1331–2 | date = May 2014 | pmid = 24443380 | pmc = 3998129 | doi = 10.1093/bioinformatics/btt772 }}
22. ^{{cite journal | vauthors = Merks RM, Guravage M, Inzé D, Beemster GT | title = VirtualLeaf: an open-source framework for cell-based modeling of plant tissue growth and development | journal = Plant Physiology | volume = 155 | issue = 2 | pages = 656–66 | date = February 2011 | pmid = 21148415 | pmc = 3032457 | doi = 10.1104/pp.110.167619 }}
23. ^{{cite journal | vauthors = Tanaka S, Sichau D, Iber D | title = LBIBCell: a cell-based simulation environment for morphogenetic problems | journal = Bioinformatics | volume = 31 | issue = 14 | pages = 2340–7 | date = July 2015 | pmid = 25770313 | doi = 10.1093/bioinformatics/btv147 | url = https://academic.oup.com/bioinformatics/article/31/14/2340/255450/LBIBCell-a-cell-based-simulation-environment-for }}
24. ^{{cite journal | vauthors = Delile J, Herrmann M, Peyriéras N, Doursat R | title = A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation | journal = Nature Communications | volume = 8 | pages = 13929 | date = January 2017 | pmid = 28112150 | pmc = 5264012 | doi = 10.1038/ncomms13929 | url = https://www.nature.com/articles/ncomms13929 }}

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