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Modeling - Activities

Objectives

  • to develop a set of integrative modeling frameworks for testing hypotheses concerning the effects of component properties (i.e. molecules) on system operation (i.e. cell migration behaviors)
  • initial focus will be on molecular components such as extracellular matrix adhesion factors and their receptors, soluble growth factors and their receptors, cytoskeletal elements, motor proteins, and signaling pathway intermediates

Migration Models in Development | Virtual Cell Technology Developments | Other Migration-related Models

Migration Models in Development

Process Modeling Method / Application Status / Publication Contact (Collaborators)
Actin dynamics Physico-chemical - (model of filopodial protrusion) Completed - Mogilner and Rubinstein, 2005 Mogilner
Actin dynamics Physico-chemical - (model of adhesion dynamics) Completed - Choi et al., 2008 Mogilner (Horwitz)
Actin dynamics Physico-chemical - (tethered polymerization ratchet model of protrusive force generation) Completed - Mogilner and Oster, 2003 Mogilner
Actin dynamics Virtual Cell - (actin dynamics at the leading edge of locomoting cells) Completed - Novak et al., 2008, CMC Update article Loew (Novak, Slepchecko, Mogilner)
Actin dynamics Physico-chemical - (model of actin dynamics in vitro) Completed - Fass et al., 2008 Mogilner (Bamburg)
Actin dynamics Physico-chemical - (model of actin dynamics and cell shape at the leading edge of the migrating keratocyte cell) Completed - Grimm et al., 2003 Mogilner
Actin dynamics Physico-chemical - (model of actin dynamics and cell shape at the leading edge of the migrating keratocyte cell) Completed - Lacayo et al., 2007, CMC Update article Mogilner (Theriot)
Actin dynamics Physico-chemical - (model of bi-stability of keratocyte lamellipodial fragments) Completed - Kozlov and Mogilner, 2007 Mogilner
Actin dynamics Physico-chemical - (1-D model of actin transport in rapidly and steadily migrating cells using partial differential equations) Completed - Mogilner and Edelstein-Keshet, 2002 Mogilner
Adhesion Physico-chemical - (model of assembly and dynamics of adhesions, stress fibers and corresponding regulatory systems) Completed - Novak et al., 2004 Mogilner (Loew)
Adhesion Physico-chemical - (modeling of focal adhesion and stress fiber dynamics) Completed - Novak et al., 2004 Loew
Adhesion, Protrusion Physico-chemical - (model of limiting role of adhesion in cell protrusion) Completed - Bohnet et al., 2006 Mogilner (Verkhovsky)
Adhesion signaling Physico-chemical - (model of cytoskeleton & Rho GTPase response to external force in endothelial cells using differential equations) Completed - Civelekoglu-Scholey et al., 2005 Mogilner (Schwartz)
Cell migration Dynamical systems model for cell/substratum adhesion linkages Completed - Macdonald et al., 2008 Lauffenburger (Horwitz)
Cell migration Development of materials that control ligand spacing independent of tether length Completed - Kuhlman et al., 2007, CMC Update article Griffith (Mayes)
Cell migration Develop a basic graphic interface to build and simulate a CMAP based on cell biology data. Completed - software available, instructional video. Jacobson (Weinreb)
Cell migration Extension of model for cell migration in 3D environments to include matrix protease effects Completed - Kim et al., 2008; Zaman et al., 2006, CMC Update article Lauffenburger (Zaman)
Cell migration Physico-chemical - (1-D model of crawling nematode sperm cell using partial differential equations on a free boundary domain) Completed - Mogilner and Verzi, 2003; Wolgemuth et al., 2004 Mogilner
Cell migration Causal mapping (CMAP) Semi-quantitative intermediate model for cytoskeletal oscillations. Develop ODE model to test CMAP formalism. Models applicable to mechano-chemical signaling in general. Completed - Weinreb et al., 2006, CMC Update Aug 06; Kapustina et al., 2008; Weinreb and Cao, 2007 Jacobson (Weinreb, Elston)
Cell migration Experimental test of model for cell migration in 3-D environments Completed - Harley et al., 2008; Zaman et al., 2006, CMC Update article Lauffenburger (Zaman)
Cell migration Physico-chemical - (2-D model of crawling keratocyte cell using Finite Element method on a free boundary domain) Completed - Rubinstein et al., 2005, view the movies (based on the model of this paper) of the motile lamellipodial fragment and of the turning lamellipodial fragment Mogilner (Jacobson)
Cell migration Force-based - (model for cell migration through 3-D matrices to model effects of cell and matrix properties on migration speed) Completed - Zaman et al., 2005 Lauffenburger (Matsudaira, Kamm)
Cell migration Physico-chemical - (1-D model of crawling cell with visco-elastic contractile lamellipodium on a free boundary domain) Completed - Larripa and Mogilner, 2006 Mogilner (Larripa)
Cell migration Physico-chemical - (2-D model of crawling nematode sperm cell using Monte Carlo simulations) Completed - Bottino et al., 2002 Mogilner
Cell Migration Studying CMAP properties such as dependence of the simulation results on set size K, concept time response constant , etc. using CMAP model of cortical oscillation. Completed - web-posting of the results is underway. Jacobson (Weinreb)
Cell Migration Modeling EGF signaling network using CMAP. Developing models binding and enzymatic reactions within CMAP approach. Use them as building blocks of a signaling network. Completed - manuscript in preparation. Jacobson (Weinreb & Bankaitis)
Cell migration signaling Physico-chemical - (model of chemotactic collective cell movement using partial differential equations) Completed - Luca et al., 2003 Mogilner
Cell shape Physico-chemical - (model of the keratocyte cell shape) Completed - Keren et al., 2008, CMC Update article Mogilner (Theriot)
Protrusion Biophysical measurement of lamellipodial protrusive force and force velocity relationship Completed - Prass et al., 2006 Jacobson, Mogilner (Prass, Radmacher)
Protrusion Physico-chemical - (model of limiting role of arginylation of beta-actin in cell protrusion) Completed - Karakozova et al., 2006 Mogilner (Kashina)
Protrusion, Actin transport Physico-chemical - (model of fluid flow of cytoplasm in migrating cells) Completed - Model in Virtual Cell. Mogilner, Loew
Signaling Macroscopic model of cell morphology control of cell polarization/migration signaling Completed - Haugh, 2007 Haugh
Signaling Detailed, domain-based model of PI 3-kinase recruitment Completed - Barua et al., 2008 Haugh (Faeder)
Signaling Bayesian network - (modeling applied to signaling pathways to model cell differentiation regulatory networks) Completed - Sachs et al., 2002; Woolf et al., 2005 Lauffenburger
Signaling Model of spatially defined growth factor receptor and integrin signaling Completed - Schneider and Haugh, 2005 Haugh
Signaling Virtual Cell - (PIP2 Turnover & PHd1-GFP translocation) Completed - Xu et al., 2003 Loew
Signaling Spatial model of PI 3-kinase signaling with realistic cell geometries Completed - Schneider et al., 2005 Haugh
Signaling Virtual Cell - (InsP3-mediated Ca++ release) Completed - Fink et al., 1999; Fink et al., 2000 Loew
Signaling Decision tree methodology for cue-signal-response Completed - Kharait et al., 2007, CMC Update article Lauffenburger
Signaling Cue-signal-response - (model using PCA/PLS methodology in cell death to model apoptosis regulatory networks) Completed - Janes et al., 2003; Janes et al., 2004 Lauffenburger
Signaling Microscopic model of reactions/interactions in cell membranes Completed - Monine and Haugh, 2005 Haugh
Signaling Microscopic model of PI 3 kinase/small GTPase signaling Completed - Monine and Haugh, 2008, CMC Update article Haugh (Schwartz, Horwitz)
Signaling Decision tree methodology for cue-signal-response - (analysis applied to signaling pathways to model cell migration responses to growth factors and extracellular matrix) Completed - Hautaniemi et al., 2005 Lauffenburger (Wells)
Actin dynamics Virtual Cell - (actin dynamics at the leading edge of locomoting cells) Completed, publication in progress Loew (Pollard)
Adhesion Physico-chemical - (model of adhesion dynamics) Completed, publication in progress Horwitz, Mogilner
Protrusion Level set/Motility of nematode sperm Completed, publication in progress Loew (Wolgemuth)
Actin dynamics Statistical analysis - (of the causality between regulatory signals, cytoskeleton dynamics and cell protrusion) In progress - Machacek and Danuser, 2006 Danuser (Hahn, Ginsberg)
Actin dynamics Physico-chemical - (mesoscopic model of force generation and symmetry breaking in actin gels) In progress Mogilner (Mullins)
Adhesion Virtual Cell - (analysis and modeling of quantitative imaging experiments on assembly/disassembly of adhesion complexes) In progress Loew (Horwitz)
Adhesion Physico-chemical - (stochastic modeling of the dynamics of focal adhesions and stress fibers) In progress Loew (Novak, Slepchenko)
Adhesion, Actin dynamics Computational image modeling of actin and adhesion dynamics in living cells In progress - Cserni et al., 2004; Hu et al., 2007, CMC Update article; Yam et al., 2007, CMC Update article; Delorme et al., 2007, CMC Update article Danuser (Waterman, Bokoch, Theriot, Forscher)
Adhesion, Actin dynamics Continuum mechanical model - (of integrated adhesion and contraction forces in lamella of migrating cells) In progress - studies completed, publication pending. Danuser
Cell migration Apply 2-D cue-signal-response migration model In progress Griffith, Lauffenburger (Horwitz, Wells)
Cell migration Apply 3-D matrices to theory-experiment cycle In progress Griffith (Wells, Gertler)
Cell migration Develop synthetic 3-D matrices that control sterics/porosity, mechanics, adhesion, proteolysis In progress Griffith
Cell Migration Develop an algorithm to acquire and implement this algorithm within the basic software. Develop a Java-based web utility through the WWW. In progress Jacobson (Weinreb)
Cell Migration Developing two-sided CMAP to include spatial aspects of cell shape oscillations. The model is based on the CMAP published earlier. In progress - Web-posting of the results is underway. Jacobson (Weinreb)
Signaling Virtual Cell - (modeling of FRAP experiments for membrane translocation of Rac) In progress Loew (Slepchenko, Schwartz)
Signaling Macroscopic, Virtual Cell models of Rac/Pak signaling and adhesion/protrusion dynamics In progress Haugh (Horwitz, Schwartz, Hahn, Danuser, Loew)
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Virtual Cell Technology Developments

Process Model Development Status / Publication Contact (Collaborators)
Virtual Cell PDGF gradient sensing Completed - now available through the Virtual Cell. Haugh (Schneider)
Virtual Cell Cell shape control Completed - now available through the Virtual Cell. Haugh
Virtual Cell Enhancement & testing of the Virtual Cell C++ library for solving diffusion-advection system of equations. Completed - now available through the Virtual Cell. Loew
Virtual Cell Development of a new minilibrary that implements the Gibson-Bruck version of the Gilespie algorithm for non-spatial stochastic simulations & testing the stochastic algorithm against exact solutions Completed - now available through the Virtual Cell. Loew
Virtual Cell Bringing the 'advection capability' to the math workspace of the user interface Completed - now available through the Virtual Cell. Loew
Virtual Cell Treatment of lateral diffusion on a curved membrane surface Completed - now available through the Virtual Cell. Loew (Novak, Slepchenko)
Virtual Cell Reaction-diffusion-convection of G-actin in 3-D cell Completed - - now available through the Virtual Cell. (Novak, Slepchenko)
Virtual Cell Darcy flow of the cytoplasm in the lamellipodium Completed - - now available through the Virtual Cell. (Slepchenko)
Virtual Cell Level set method In progress Loew (Wolgemuth)
Virtual Cell Enhancement of the VC library to allow solving for the velocity field Under consideration Loew
Virtual Cell Implementing Monte-Carlo type algorithms for spatial stochastic simulation Under consideration Loew
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CMC is a public account in the Virtual Cell database of models. It can be accessed by any user by logging into the Virtual Cell Website

Other Migration Related Models

Process Modeling Method / Application Publication
Adhesion Dynamics Quantitative Ward et al., 1994
Adhesion Dynamics Combined Modeling & Experiments Palecek et al., 1999
Cell migration Combined Modeling & Experiments Heid et al., 2002, Lee et al., 1999
Cell migration Quantitative Bottino et al., 2002, DiMilla et al., 1991, Evans, 1993, He and Dembo, 1997, Oster and Perelson, 1987
Contraction & mechanics of the cytoskeleton Quantitative Alt and Dembo, 1999, Bottino and Fauci, 1998, Dembo, 1989, Oster and Odell, 1984
Protrusion & the Leading Edge Quantitative Carlsson, 2001, Dickinson and Purich, 2002, Gerbal et al., 2000, Mogilner and Oster, 1996
Protrusion & the Leading Edge Quantitative Laurent et al., 1999
Regulation of motility & actin turnover Quantitative Dufort and Lumsden, 1993, Dufort and Lumsden, 1996, Edelstein-Keshet, 1998, Levchenko and Iglesias, 2002
Regulation of motility & actin turnover Combined Modeling & Experiments Carlier and Pantaloni, 1997, Fang et al., 1999, Roy et al., 2001
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