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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

Collaboration and Release Policy

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

Migration Models in Development

Process Modeling Method / Application Status / Publication Contact (Collaborators)
Protrusion Level set/Motility of nematode sperm Biophys J. in press Wolgemuth
Cell Migration Develop a basic graphic interface to build and simulate a CMAP based on cell biology data. Completed Jacobson (Weinreb)
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 - Kapustina et al., 2008 - in press. Weinreb & Cao, Weinreb et al., 2006 CMC Update Aug 06 Jacobson (Weinreb, Elston)
Protrusion and actin transport Physico-chemical model of fluid flow of cytoplasm in migrating cells Completed - Model in Virtual Cell Mogilner, 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., 2004 Mogilner (Schwartz)
Signaling Virtual Cell - InsP3-mediated Ca++ release Completed - Fink et al., 1999, Fink et al., 2000 Loew
Cell migration signaling Physico-chemical model of chemotactic collective cell movement using partial differential equations Completed - Luca et at., 2003 Mogilner
Signaling Spatial model of PI 3-kinase signaling with realistic cell geometries Completed - Schneider et al., 2005 Haugh
Adhesion Physico-chemical model of adhesion dynamics Completed - publication in progress Mogilner, Horwitz
Actin dynamics Virtual Cell - Actin dynamics at the leading edge of locomoting cells Completed - publication in review Loew (Pollard)
Protrusion Physico-chemical model of limiting role of arginylation of beta-actin in cell protrusion Completed - Karakozova et al, 2006 Mogilner (Kashina)
Protrusion Biophysical measurement of lamellipodial protrusive force and force velocity relationship Completed - Prass et al, 2006 Mogilner, Jacobson (Prass, Radmacher)
Signaling Detailed, domain-based model of PI 3-kinase recruitment Completed - Barua, et al.,2008 Haugh (J. Faeder, Univ. of Pittsburgh)
Cell migration Physico-chemical 2D model of crawling nematode sperm cell using Monte Carlo simulations Completed - Bottino, et al.,2002 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
Signaling Macroscopic model of cell morphology control of cell polarization/migration signaling Completed - Haugh, 2007 Haugh
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)
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 Completed - Kharait et al, 2007 Lauffenburger
Actin dynamics Physico-chemical model of bi-stability of keratocyte lamellipodial fragments Completed - Kozlov MM, Mogilner A, 2007 Mogilner
Cell Migration Development of materials that control ligand spacing independent of tether length Completed - Kuhlman et al., 2007, CMC Update Griffith, (Mayes et al)
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 Larripa (Mogilner)
Cell migration Dynamical systems model for cell/substratum adhesion linkages Completed - MacDonald, et al.,2008 In press Lauffenburger (Horwitz)
Actin dynamics Physico-chemical 1D model of actin transport in rapidly and steadily migrating cells using partial differential equations Completed - Mogilner and Edelstein-Keshet 2002 Mogilner
Actin dynamics Physico-chemical model of filopodial protrusion Completed - Mogilner and Rubinstein, 2005 Mogilner
Actin dynamics Physico-chemicalmodel of actin dynamics and cell shape at the leading edge of the migrating keratocyte cell Completed - Mogilner and Theriot, 2007 Mogilner (Theriot)
Cell Shape Physico-chemical model of the keratocyte cell shape Completed - Mogilner and Theriot, 2008 Mogilner (Theriot)
Cell migration Physico-chemical 1D 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
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 Haugh (Schwartz, Horwitz)
Adhesion Physico-chemical modeling of focal adhesion and stress fiber dynamics Completed - Novak et al., 2004 Loew
Adhesion Physico-chemical model of assembly and dynamics of adhesions, stress fibers and corresponding regulatory systems Completed - Novak et al., 2004 Mogilner (Loew)
Actin dynamics Virtual Cell - Actin dynamics at the leading edge of locomoting cells Completed - Novak et al.,2008 Novak, Slepchecko (Mogilner)
Signaling Bayesian network modeling applied to signaling pathways to model cell differentiation regulatory networks Completed - Sachs et al., 2002 Woolf et al., 2004 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
Cell migration Force-based model for cell migration through 3D matrices to model effects of cell and matrix properties on migration speed. Completed - Zaman et al., 2005 Lauffenburger (Matsudaira & Kamm)
Cell Migration Experimental test of model for cell migration in 3D environments Completed - Zaman et al., 2006 Harley, et al.,2008 Lauffenburger (Zaman, et al.)
Cell migration Physico-chemical 2 D model of crawling keratocyte cell using Finite Element method on a free boundary domain Completed -B. Rubinstein et al., 2005. View the movies (based on the model of this paper) of the motile lamellipodial fragment here and of the turning lamellipodial fragment here. Mogilner (Jacobson)
Actin dynamics Physico-chemical tethered polymerization ratchet model of protrusive force generation Completed -Mogilner and Oster 2003 Mogilner
Cell Migration Extension of model for cell migration in 3D environments to include matrix protease effects Completed -Zaman, et al.,2006;Kim, et al.,2008 Lauffenburger (Zaman, et al.)
Actin dynamics Physico-chemical mesoscopic model of force generation and symmetry breaking in actin gels In progress Mogilner (Mullins)
Adhesion Virtual Cell - Analysis & 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
Cell migration Develop synthetic 3D matrices that control sterics/porosity, mechanics, adhesion, proteolysis In progress Griffith
Cell migration Apply 3D matrices to theory-experiment cycle. In progress Griffith, (Wells, Gertler)
Cell Migration Develop an algorithm to acquire expert opinions and implement this algorithm within the basic software. Develop a Java-based web utility to acquire expert opinions through the WWW. In progress Jacobson (Weinreb)
Cell migration Apply 2D cue-signal-response migration model In progress Lauffenburger, Griffith, (Horwitz, Wells)
Signaling Macroscopic, Virtual Cell models of Rac/Pak signaling and adhesion/protrusion dynamics In progress Haugh (Horwitz, Schwartz, Hahn, Danuser, Loew)
Signaling Virtual Cell - Modeling of FRAP experiments for membrane translocation of Rac In progress Slepchenko (Schwartz)
Adhesion, Actin dynamics Continuum mechanical model of integrated adhesion and contraction forces in lamella of migrating cells In progress - studies completed, publication pending Danuser
Actin dynamics Statistical analysis of the causality between regulatory signals, cytoskeleton dynamics and cell protrusion In progress; published to date - Machacek and Danuser, 2006 Danuser (Hahn & Ginsberg)
Adhesion Actin dynamics Computational image modeling of actin and adhesion dynamics in living cells In progress; published to date- Ponti et al.,2004, Hu et al, 2007 (Feb 2007 Update), Yam et al., 2007 (Nov 2007 Update), Delorme et al., 2007 (Featured Article, Dec 2007) Danuser (Waterman; Bokoch; Theriot; Forscher)
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Virtual Cell Technology Developments

Process Model Development Status / Publication Contact (Collaborators)
Virtual Cell PDGF gradient sensing now available through the Virtual Cell Schneider &Haugh
Virtual Cell Cell shape control now available through the Virtual Cell Haugh
Virtual Cell Enhancement & testing of the Virtual Cell C++ library for solving diffusion-advection system of equations. 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 now available through the Virtual Cell Loew
Virtual Cell Bringing the 'advection capability' to the math workspace of the user interface now available through the Virtual Cell Loew
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
Virtual Cell Treatment of lateral diffusion on a curved membrane surface now available through the Virtual Cell Slepchenko, Novak
Virtual Cell Level set method In progress Wolgemuth
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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 Type Publication
Adhesion Dynamics Quantitative Ward MD, et al., 1994
Adhesion Dynamics Combined Modeling & Experiments Palecek SP et al., 1999
Contraction & mechanics of the cytoskeleton Quantitative Alt and Dembo 1999, Bottino and Fauci 1998, Dembo M. 1989, Oster and Odell 1984
Protrusion & the Leading Edge Quantitative Laurent V et al., 1999
Protrusion & the Leading Edge Quantitative Carlsson 2001, Dickinson and Purich 2002, Gerbal et al., 2000, Mogilner and Oster 1996
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
Cell migration Quantitative Bottino et al., 2002, DiMilla et al., 1991,Evans 1993, He and Dembo 1997, Oster and Perelson 1987
Cell migration Combined Modeling & Experiments Heid et al., 2002, Lee J, et al., 1993
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