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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 Developmed | Virtual Cell Technology Developments | Other Migration-related Models

Migration Models Developed

Process Modeling Method / Application Status / Publication Contact (Collaborators)
Actin dynamics Physico-chemical - (mesoscopic model of force generation and symmetry breaking in actin gels) Completed - Dayel et al., 2009 Mogilner (Mullins)
Actin dynamics Virtual cell - (actin dynamics at the leading edger of locomoting cells) Completed - Novak et al., 2008 (CMC Update Article) Loew (Novak, Slepchecko)
Actin dynamics Virtual Cell - (actin dynamics at the leading edge of locomoting cells) Completed - Kraikivski and Slepchenko, 2010 Loew
Actin dynamics Virtual Cell - (actin dynamics at the leading edge of locomoting cells) Completed - Ditlev et al., 2009 (CMC Update Article) Loew (Novak, Slepchecko, 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 (CMC Update Article) 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 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 in vitro) Completed - Fass et al., 2008 Mogilner (Bamburg)
Actin dynamics Physico-chemical - (model of adhesion dynamics) Completed - Choi et al., 2008 (CMC Update Article) Mogilner (Horwitz)
Actin dynamics Physico-chemical - (model of bi-stability of keratocyte lamellipodial fragments) Completed - Kozlov and Mogilner, 2007 (CMC Update Article) Mogilner
Actin dynamics Physico-chemical - (model of filopodial protrusion) Completed - Mogilner and Rubinstein, 2005 (CMC Update Article) Mogilner
Actin dynamics Physico-chemical - (tethered polymerization ratchet model of protrusive force generation) Completed - Mogilner and Oster, 2003 Mogilner
Adhesion Physico-chemical - (modeling of focal adhesion and stress fiber dynamics) Completed - Novak et al., 2004 Loew (Mogilner)
Adhesion Physico-chemical - (model of adhesion dynamics) Completed Horwitz, Mogilner
Adhesion Physico-chemical - (stochastic modeling of the dynamics of focal adhesions and stress fibers) Completed Loew (Novak, Slepchenko)
Adhesion Virtual Cell - (analysis and modeling of quantitative imaging experiments on assembly/disassembly of adhesion complexes) Completed Loew (Horwitz)
Adhesion, Actin dynamics Computational image modeling of actin and adhesion dynamics in living cells Completed - Burnette et al., 2007; Delorme et al., 2007 (CMC Update Article); Hu et al., 2007 (CMC Update Article); Yam et al., 2007 (CMC Update Article); Schaefer et al., 2008 (CMC Update Article); Wilson et al., 2010 Danuser (Waterman, Bokoch, Theriot, Forscher)
Adhesion, Actin dynamics Continuum mechanical model - (of integrated adhesion and contraction forces in lamella of migrating cells) Completed - Ji et al., 2007 (CMC Update Article); Ji et al., 2008 (CMC Update Article) Danuser
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 (CMC Update Article) Mogilner (Schwartz)
Cell migration Apply 2-D cue-signal-response migration model Completed - Meyer et al., 2012 Griffith, Lauffenburger (Horwitz, Wells)
Cell migration Apply 3-D matrices to theory-experiment cycle Completed - Kim et al., 2008 Griffith (Wells, Gertler)
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 Develop synthetic 3-D matrices that control sterics/porosity, mechanics, adhesion, proteolysis Completed Griffith
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 Article); Weinreb and Cao, 2007; Kapustina et al., 2008; Weinreb et al., 2009 (CMC Update Article) Jacobson (Weinreb, Elston)
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 Dynamical systems model for cell/substratum adhesion linkages Completed - Macdonald et al., 2008 (CMC Update Article) Lauffenburger (Horwitz)
Cell migration Experimental test of model for cell migration in 3-D environments Completed - Zaman et al., 2006 (CMC Update Article); Harley et al., 2008 (CMC Update Article) Lauffenburger (Zaman)
Cell migration Extension of model for cell migration in 3D environments to include matrix protease effects Completed - Zaman et al., 2006 (CMC Update Article); Kim et al., 2008 Lauffenburger (Zaman)
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 (CMC Update Article) 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 - (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 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 Physico-chemical - (2-D model of crawling nematode sperm cell using Monte Carlo simulations) Completed - Bottino et al., 2002 Mogilner
Cell Migration Develop an algorithm to acquire and implement this algorithm within the basic software. Develop a Java-based web utility through the WWW. Completed Jacobson (Weinreb)
Cell Migration Developing two-sided CMAP to include spatial aspects of cell shape oscillations. Model based on the CMAP published previously. Completed 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 Jacobson (Weinreb & Bankaitis)
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 - Weinreb et al., 2009 (CMC Update Article) Jacobson (Weinreb)
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 Level set/Motility of nematode sperm Completed - Zajac et al., 2008; Stajic and Wolgemuth, 2009 Loew (Wolgemuth)
Protrusion Virtual cell - (Model of filopdia formation regulated by capping protein and Ena/VASP) Completed - Kapustina et al., 2010 (CMC Update Article) Loew (Jacobson)
Protrusion Biophysical measurement of lamellipodial protrusive force and force velocity relationship Completed - Prass et al., 2006 (CMC Update Article) Jacobson, Mogilner (Prass, Radmacher)
Protrusion Physico-chemical - (model of limiting role of arginylation of beta-actin in cell protrusion) Completed - Karakozova et al., 2006 (CMC Update Article) Mogilner (Kashina)
Protrusion, Actin transport Physico-chemical - (model of fluid flow of cytoplasm in migrating cells) Completed - Model in Virtual Cell Loew, Mogilner
Signaling Macroscopic, Virtual Cell models of Rac/Pak signaling and adhesion/protrusion dynamics Completed Haugh (Horwitz, Schwartz, Hahn, Loew)
Signaling Stochastic models of Rac/Pak signaling and adhesion/protrusion dynamics Completed - Cirit et al., 2010 (CMC Update Article); Welf and Haugh, 2010 (CMC Update Article) Haugh (Horwitz)
Signaling Virtual Cell - (analysis of diffusion in crowded environments) Completed - Novak et al., 2009 Loew
Signaling Virtual Cell - (InsP3-mediated Ca++ release) Completed - Fink et al., 1999; Fink et al., 2000 Loew
Signaling Virtual Cell - (modeling of FRAP experiments for membrane translocation of Rac) Completed - Moissoglu et al., 2006 (CMC Update Article) Loew (Slepchenko, Schwartz)
Signaling Bayesian network - (modeling applied to signaling pathways to model cell differentiation regulatory networks) Completed - Sachs et al., 2002 (CMC Update Article); Woolf et al., 2005 (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 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 (CMC Update Article) Lauffenburger (Wells)
Signaling Decision tree methodology for cue-signal-response Completed - Kharait et al., 2007 (CMC Update Article) Lauffenburger
Signaling Detailed, domain-based model of PI 3-kinase recruitment Completed - Barua et al., 2008 Haugh (Faeder)
Signaling Macroscopic model of cell morphology control of cell polarization/migration signaling Completed - Haugh, 2007 (CMC Update Article) Haugh
Signaling Microscopic model of PI 3 kinase/small GTPase signaling Completed - Codes Available, Monine and Haugh, 2008 (CMC Update Article) Haugh (Schwartz, Horwitz)
Signaling Microscopic model of reactions/interactions in cell membranes Completed - Codes Available, Monine and Haugh, 2005 (CMC Update Article) Haugh
Signaling Model of spatially defined growth factor receptor and integrin signaling Completed - Schneider and Haugh, 2005 (CMC Update Article) Haugh
Signaling Spatial model of PI 3-kinase signaling with realistic cell geometries Completed - Schneider et al., 2005 (CMC Update Article) Haugh
Signaling Virtual Cell - (PIP2 Turnover & PHd1-GFP translocation) Completed - Xu et al., 2003 Loew
Signaling Dynamics Statistical analysis - (of the causality between regulatory signals, cytoskeleton dynamics and cell protrusion) Completed - Machacek and Danuser, 2006 (CMC Update Article); Sabouri-Ghomi et al., 2008 (CMC Update Article); Machacek et al., 2009 (CMC Update Article) Danuser (Hahn, Ginsberg)
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Virtual Cell Technology Developments

Process Model Development Status / Publication Contact (Collaborators)
Virtual Cell Bringing the 'advection capability' to the math workspace of the user interface Completed - now available through the Virtual Cell Loew
Virtual Cell Darcy flow of the cytoplasm in the lamellipodium Completed - now available through the Virtual Cell and published Novak et al., 2009 (Slepchenko)
Virtual Cell Enhancement of the VC library to allow solving for the velocity field Completed - now available through the Virtual Cell Loew
Virtual Cell Implementing Monte-Carlo type algorithms for spatial stochastic simulation Completed - now available through the Virtual Cell Loew
Virtual Cell Level set method Completed - Available through the Virtual Cell and published Wolgemuth and Zajac, 2010 Loew (Wolgemuth)
Virtual Cell Reaction-diffusion-convection of G-actin in 3-D cell Completed - Available through the Virtual Cell and published Novak et al., 2008 (CMC Update Article); Novak et al., 2009; Novak et al., 2011 (Novak, Slepchenko)
Virtual Cell Treatment of lateral diffusion on a curved membrane surface Completed - now available through the Virtual Cell Loew (Novak, Slepchenko)
Virtual Cell Cell shape control Completed - now available through the Virtual Cell Haugh
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 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 PDGF gradient sensing Completed - now available through the Virtual Cell Haugh (Schneider)
Virtual Cell Virtual FRAP: Software for analysis and simulation of FRAP experiments. Completed - Moraru et al., 2008; Kapustina et al., 2010 (CMC Update Article) Loew (Schaff)
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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 Combined Modeling & Experiments Palecek et al., 1999
Adhesion Dynamics Quantitative Ward et al., 1994
Cell migration Combined Modeling & Experiments Lee et al., 1999, Heid et al., 2002
Cell migration Quantitative Oster and Perelson, 1987, DiMilla et al., 1991, Evans, 1993, He and Dembo, 1997, Bottino et al., 2002
Contraction & mechanics of the cytoskeleton Quantitative Oster and Odell, 1984, Dembo, 1989, Bottino and Fauci, 1998, Alt and Dembo, 1999
Protrusion & the Leading Edge Quantitative Laurent et al., 1999
Protrusion & the Leading Edge Quantitative Mogilner and Oster, 1996, Gerbal et al., 2000, Carlsson, 2001, Dickinson and Purich, 2002
Regulation of motility & actin turnover Combined Modeling & Experiments Carlier and Pantaloni, 1997, Fang et al., 1999, Roy et al., 2001
Regulation of motility & actin turnover Quantitative Dufort and Lumsden, 1993, Dufort and Lumsden, 1996, Edelstein-Keshet, 1998, Levchenko and Iglesias, 2002
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