From brunni at netestate.de Fri Jul 4 01:55:05 2014 From: brunni at netestate.de (Michael Brunnbauer) Date: Fri Jul 4 01:55:10 2014 Subject: [Compucell3d-users] Explanation for branched structures in CompuCell3D angiogenesis example In-Reply-To: References: <20140627162358.GA16790@netestate.de> Message-ID: <20140704085505.GA17794@netestate.de> Dear Walter, thank you for the pointers, which have been helpful. I think I succeeded to reproduce the effect by reducing diffusion, chemotaxis and cell adhesion by an order of magnitude (cell adhesion ratios are unchanged). Most critical was reducing the energies involved in cell adhesion, which seems to contradict results from the paper "Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling": >Variant models omitting the length constraint could produce patterns somewhat >like those obtained in vitro if we assumed very strong intercellular adhesion >or chemoattractant gradients steep relative to cell size (Fig. 9). In my simulation, reducing adhesion energies makes the cells more motile which enables them to protude extensions before the VEGF gradient sets in. The network patterns then grow out of these random extensions. You can find a complete minimal example (with animated gifs) at http://www.brunni.de/ggc/ Regards, Michael Brunnbauer On Mon, Jun 30, 2014 at 08:47:03AM +0200, Walter de Back wrote: > Dear Michael, > > The biology and math behind the emergence of network patterns has been > described in a series of publications (see below). > > The first model that showed the formation of vascular networks, based on > chemotaxis towards cell-produced VEGF, is the PDE model by Serini and > Preziosi. This model was later re-formulated and extended into a cell-based > CPM model (in Compucell3D) by Merks and Glazier. Based on this hybrid > CPM/PDE model (but simulated in Morpheus instead of Compucell3D), > K?hn-Luque and myself showed more recently that network formation is also > possible under the biologically more realistic assumption of paracrine > production of VEGF (i.e. surrounding tissue produce VEGF) together with > binding of VEGF to extracellular matrix components. > > In essence, you want to create steep gradients of chemoattractant around > cells. In the autocrine model, this requires a certain ratio balance > between diffusion (typically unrealistically low) and decay. In the > paracrine model, network formation is insensitive to the diffusion > coefficient, and rather depends on ratio between binding and unbinding > rates. > > > Best, > Walter > > > > *Autocrine chemotaxis in PDE model:* > > G. Serini, D. Ambrosi, E. Giraudo, A. Gamba, L. Preziosi, F. > Bussolino. Modelling > the early stages of vascular network assembly > , EMBO J. 22:1771-1779, 2003. > > *Autocrine chemotaxis in CPM / PDE model:* > > Roeland M.H. Merks, Sergey V. Brodsky, Michael S. Goligorsky, Stuart A. > Newman, and James A. Glazier. 2006. Cell elongation is key to in silico > replication of in vitro vasculogenesis and subsequent remodeling. > Developmental Biology, 289(1), 44-54. > > Roeland M.H. Merks and James A. Glazier. 2006. Dynamic mechanisms of blood > vessel growth. Nonlinearity, 19, C1-C10. > > Roeland M.H. Merks, Erica D. Perryn, Abbas Shirinifard and James A. > Glazier. 2008. Contact-inhibited chemotactic motility in de novo and > sprouting blood vessel growth. PLoS Computational Biology 4(9): e1000163, > 2008. > > *Paracrine chemotaxis in CPM / PDE model:* > > A. K?hn-Luque, W. de Back, J. Starru?, A. Mattiotti, A. Deutsch, J. M. > P?rez-Pomares, M. A. Herrero. Early Embryonic Vascular Patterning by > Matrix-Mediated Paracrine Signalling. PLoS ONE 6(9):e24175, 2011. > > A. K?hn-Luque, W. de Back, Y. Yamaguchi, K. Yoshimura, M. A. Herrero and T. > Miura. Dynamics of VEGF Matrix-Retention in Vascular Network > Patterning. Physical Biology, 10:066007, 2013. -- ++ Michael Brunnbauer ++ netEstate GmbH ++ Geisenhausener Stra?e 11a ++ 81379 M?nchen ++ Tel +49 89 32 19 77 80 ++ Fax +49 89 32 19 77 89 ++ E-Mail brunni@netestate.de ++ http://www.netestate.de/ ++ ++ Sitz: M?nchen, HRB Nr.142452 (Handelsregister B M?nchen) ++ USt-IdNr. DE221033342 ++ Gesch?ftsf?hrer: Michael Brunnbauer, Franz Brunnbauer ++ Prokurist: Dipl. Kfm. (Univ.) Markus Hendel -------------- next part -------------- A non-text attachment was scrubbed... Name: not available Type: application/pgp-signature Size: 198 bytes Desc: not available Url : https://simtk.org/pipermail/compucell3d-users/attachments/20140704/ef620899/attachment.bin