The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Ravi Iyengar - One of the best experts on this subject based on the ideXlab platform.
-
Membrane Feedback Controls Signaling Regulation of Cell Spreading
Biophysical Journal, 2011Co-Authors: Padmini Rangamani, Michael P. Sheetz, Marc-antoine Fardin, Olivier Rossier, Yuguang Xiong, Azi Lipshtat, Ravi IyengarAbstract:Cell motility and Spreading are regulated by signaling from the integrin receptors. Interaction between the integrin receptors and substrates such as fibronectin triggers the activation of downstream signaling pathways, resulting in the activation of actin regulating proteins such as Arp2/3, gelsolin and profilin. We have developed an integrated model of Cell Spreading regulated by integrin signaling network to understand the role of signaling during fast isotropic Spreading, when fibroblasts spread on fibronectin coated slides. The three dimensional stochastic Spreading model was developed using differential geometry techniques and is coupled with a deterministic model for integrin signaling regulation. We find that Cell Spreading is a robust process and depends on signaling only for the initiation of Spreading but not for maintaining the Spreading dynamics. Our model further predicts that signaling dynamics in the absence of Cdc42 and WASP reduce the Spreading rate to a small extent but do not affect the shape evolution of the Spreading Cell. These predictions were verified by experiments conducted with dominant negative Cdc42 Cells and wiskostatin effects on Cell Spreading. Computational analyses predicted that the Spreading shape evolution is controlled by the physical properties of the plasma membrane such as membrane surface load and membrane bending ridigity. Simulations from our model identified that changing these properties affects the Spreading dynamics, in particular the shape evolution. In contrast, changing information flow through the Cell signaling network has little effect. Overall isotropic fast Spreading of fibroblasts on fibronectin-coated surfaces depends strongly on the biophysical properties of the plasma membrane and is robust to changes in the signaling dynamics.
-
Cell Spreading as a hydrodynamic process
Soft matter, 2010Co-Authors: Marc-antoine Fardin, Olivier Rossier, Padmini Rangamani, P. D. Avigan, Nils C. Gauthier, W. Vonnegut, Anurag Mathur, James Hone, Ravi Iyengar, Michael P. SheetzAbstract:Many Cell types have the ability to move themselves by crawling on extra-Cellular matrices. Although Cell motility is governed by actin and myosin filament assembly, the pattern of the movement follows the physical properties of the network ensemble average. The first step of motility, Cell Spreading on matrix substrates, involves a transition from round Cells in suspension to polarized Cells on substrates. Here we show that the Spreading dynamics on 2D surfaces can be described as a hydrodynamic process. In particular, we show that the transition from isotropic Spreading at early time to anisotropic Spreading is reminiscent of the fingering instability observed in many Spreading fluids. During Cell Spreading, the main driving force is the polymerization of actin filaments that push the membrane forward. From the equilibrium between the membrane force and the cytoskeleton, we derive a first order expression of the polymerization stress that reproduces the observed behavior. Our model also allows an interpretation of the effects of pharmacological agents altering the polymerization of actin. In particular we describe the influence of Cytochalasin D on the nucleation of the fingering instability.
-
A three-dimensional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D) that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.
-
A Three dimesional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well-characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D)that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.
Michael P. Sheetz - One of the best experts on this subject based on the ideXlab platform.
-
Membrane Feedback Controls Signaling Regulation of Cell Spreading
Biophysical Journal, 2011Co-Authors: Padmini Rangamani, Michael P. Sheetz, Marc-antoine Fardin, Olivier Rossier, Yuguang Xiong, Azi Lipshtat, Ravi IyengarAbstract:Cell motility and Spreading are regulated by signaling from the integrin receptors. Interaction between the integrin receptors and substrates such as fibronectin triggers the activation of downstream signaling pathways, resulting in the activation of actin regulating proteins such as Arp2/3, gelsolin and profilin. We have developed an integrated model of Cell Spreading regulated by integrin signaling network to understand the role of signaling during fast isotropic Spreading, when fibroblasts spread on fibronectin coated slides. The three dimensional stochastic Spreading model was developed using differential geometry techniques and is coupled with a deterministic model for integrin signaling regulation. We find that Cell Spreading is a robust process and depends on signaling only for the initiation of Spreading but not for maintaining the Spreading dynamics. Our model further predicts that signaling dynamics in the absence of Cdc42 and WASP reduce the Spreading rate to a small extent but do not affect the shape evolution of the Spreading Cell. These predictions were verified by experiments conducted with dominant negative Cdc42 Cells and wiskostatin effects on Cell Spreading. Computational analyses predicted that the Spreading shape evolution is controlled by the physical properties of the plasma membrane such as membrane surface load and membrane bending ridigity. Simulations from our model identified that changing these properties affects the Spreading dynamics, in particular the shape evolution. In contrast, changing information flow through the Cell signaling network has little effect. Overall isotropic fast Spreading of fibroblasts on fibronectin-coated surfaces depends strongly on the biophysical properties of the plasma membrane and is robust to changes in the signaling dynamics.
-
Cell Spreading as a hydrodynamic process
Soft matter, 2010Co-Authors: Marc-antoine Fardin, Olivier Rossier, Padmini Rangamani, P. D. Avigan, Nils C. Gauthier, W. Vonnegut, Anurag Mathur, James Hone, Ravi Iyengar, Michael P. SheetzAbstract:Many Cell types have the ability to move themselves by crawling on extra-Cellular matrices. Although Cell motility is governed by actin and myosin filament assembly, the pattern of the movement follows the physical properties of the network ensemble average. The first step of motility, Cell Spreading on matrix substrates, involves a transition from round Cells in suspension to polarized Cells on substrates. Here we show that the Spreading dynamics on 2D surfaces can be described as a hydrodynamic process. In particular, we show that the transition from isotropic Spreading at early time to anisotropic Spreading is reminiscent of the fingering instability observed in many Spreading fluids. During Cell Spreading, the main driving force is the polymerization of actin filaments that push the membrane forward. From the equilibrium between the membrane force and the cytoskeleton, we derive a first order expression of the polymerization stress that reproduces the observed behavior. Our model also allows an interpretation of the effects of pharmacological agents altering the polymerization of actin. In particular we describe the influence of Cytochalasin D on the nucleation of the fingering instability.
-
Talin depletion reveals independence of initial Cell Spreading from integrin activation and traction
Nature cell biology, 2008Co-Authors: Xian Zhang, Guoying Jiang, Yunfei Cai, Susan J. Monkley, David R. Critchley, Michael P. SheetzAbstract:Talins link integrins to the actin cytoskeleton and are important for Cell Spreading. Sheetz and colleagues show that talin is dispensable for initial Cell Spreading but it is required for sustained Cell Spreading and adhesion.
-
dynamic phase transitions in Cell Spreading
Physical Review Letters, 2004Co-Authors: Hansgunther Dobereiner, Benjamin J Dubinthaler, Gregory Giannone, Harry Xenias, Michael P. SheetzAbstract:We monitored isotropic Spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents in three sequential phases, which we denote as basal, continuous, and contractile Spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the Spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continuous to contractile Spreading. We propose that the classification of Cell Spreading into phases with distinct functional characteristics and protein activity serves as a paradigm for a general program of a phase classification of Cellular phenotype.
-
Cell Spreading and lamellipodial extension rate is regulated by membrane tension
Journal of Cell Biology, 2000Co-Authors: Drazen Raucher, Michael P. SheetzAbstract:Cell Spreading and motility require the extension of the plasma membrane in association with the assembly of actin. In vitro, extension must overcome resistance from tension within the plasma membrane. We report here that the addition of either amphiphilic compounds or fluorescent lipids that expanded the plasma membrane increased the rate of Cell Spreading and lamellipodial extension, stimulated new lamellipodial extensions, and caused a decrease in the apparent membrane tension. Further, in PDGF-stimulated motility, the increase in the lamellipodial extension rate was associated with a decrease in the apparent membrane tension and decreased membrane–cytoskeleton adhesion through phosphatidylinositol diphosphate hydrolysis. Conversely, when membrane tension was increased by osmotically swelling Cells, the extension rate decreased. Therefore, we suggest that the lamellipodial extension process can be activated by a physical signal (perhaps secondarily), and the rate of extension is directly dependent upon the tension in the plasma membrane. Quantitative analysis shows that the lamellipodial extension rate is inversely correlated with the apparent membrane tension. These studies describe a physical chemical mechanism involving changes in membrane–cytoskeleton adhesion through phosphatidylinositol 4,5-biphosphate–protein interactions for modulating and stimulating the biochemical processes that power lamellipodial extension.
Padmini Rangamani - One of the best experts on this subject based on the ideXlab platform.
-
Membrane Feedback Controls Signaling Regulation of Cell Spreading
Biophysical Journal, 2011Co-Authors: Padmini Rangamani, Michael P. Sheetz, Marc-antoine Fardin, Olivier Rossier, Yuguang Xiong, Azi Lipshtat, Ravi IyengarAbstract:Cell motility and Spreading are regulated by signaling from the integrin receptors. Interaction between the integrin receptors and substrates such as fibronectin triggers the activation of downstream signaling pathways, resulting in the activation of actin regulating proteins such as Arp2/3, gelsolin and profilin. We have developed an integrated model of Cell Spreading regulated by integrin signaling network to understand the role of signaling during fast isotropic Spreading, when fibroblasts spread on fibronectin coated slides. The three dimensional stochastic Spreading model was developed using differential geometry techniques and is coupled with a deterministic model for integrin signaling regulation. We find that Cell Spreading is a robust process and depends on signaling only for the initiation of Spreading but not for maintaining the Spreading dynamics. Our model further predicts that signaling dynamics in the absence of Cdc42 and WASP reduce the Spreading rate to a small extent but do not affect the shape evolution of the Spreading Cell. These predictions were verified by experiments conducted with dominant negative Cdc42 Cells and wiskostatin effects on Cell Spreading. Computational analyses predicted that the Spreading shape evolution is controlled by the physical properties of the plasma membrane such as membrane surface load and membrane bending ridigity. Simulations from our model identified that changing these properties affects the Spreading dynamics, in particular the shape evolution. In contrast, changing information flow through the Cell signaling network has little effect. Overall isotropic fast Spreading of fibroblasts on fibronectin-coated surfaces depends strongly on the biophysical properties of the plasma membrane and is robust to changes in the signaling dynamics.
-
Cell Spreading as a hydrodynamic process
Soft matter, 2010Co-Authors: Marc-antoine Fardin, Olivier Rossier, Padmini Rangamani, P. D. Avigan, Nils C. Gauthier, W. Vonnegut, Anurag Mathur, James Hone, Ravi Iyengar, Michael P. SheetzAbstract:Many Cell types have the ability to move themselves by crawling on extra-Cellular matrices. Although Cell motility is governed by actin and myosin filament assembly, the pattern of the movement follows the physical properties of the network ensemble average. The first step of motility, Cell Spreading on matrix substrates, involves a transition from round Cells in suspension to polarized Cells on substrates. Here we show that the Spreading dynamics on 2D surfaces can be described as a hydrodynamic process. In particular, we show that the transition from isotropic Spreading at early time to anisotropic Spreading is reminiscent of the fingering instability observed in many Spreading fluids. During Cell Spreading, the main driving force is the polymerization of actin filaments that push the membrane forward. From the equilibrium between the membrane force and the cytoskeleton, we derive a first order expression of the polymerization stress that reproduces the observed behavior. Our model also allows an interpretation of the effects of pharmacological agents altering the polymerization of actin. In particular we describe the influence of Cytochalasin D on the nucleation of the fingering instability.
-
A three-dimensional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D) that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.
-
A Three dimesional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well-characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D)that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.
Nelly Kieffer - One of the best experts on this subject based on the ideXlab platform.
-
RGD, the Rho'd to Cell Spreading.
European journal of cell biology, 2005Co-Authors: Alexandre Salsmann, Elisabeth Schaffner-reckinger, Nelly KiefferAbstract:Some RGD-type integrins rely on a synergistic site in addition to the canonical RGD site for ligand binding. However, the precise involvement of each of these recognition sites during Cell adhesion is still unclear. Here we review recent investigations on integrin alphaIIbbeta3-mediated Cell adhesion to immobilized fibrinogen providing evidence that the fibrinogen synergy gamma(400-411) sequence by itself promotes Cell attachment by initiating alphaIIbbeta3 clustering and recruitment of intraCellular proteins to focal complexes, while the RGD motif subsequently acts as a molecular switch on the beta3 subunit to induce a conformational change necessary for RhoA activation and full Cell Spreading.
-
RGD, the Rho'd to Cell Spreading.
European Journal of Cell Biology, 2005Co-Authors: Alexandre Salsmann, Elisabeth Schaffner-reckinger, Nelly KiefferAbstract:Some RGD-type integrins rely on a synergistic site in addition to the canonical RGD site for ligand binding. However, the precise involvement of each of these recognition sites during Cell adhesion is still unclear. Here we review recent investigations on integrin αIIbβ3-mediated Cell adhesion to immobilized fibrinogen providing evidence that the fibrinogen synergy γ400–411 sequence by itself promotes Cell attachment by initiating αIIbβ3 clustering and recruitment of intraCellular proteins to focal complexes, while the RGD motif subsequently acts as a molecular switch on the β3 subunit to induce a conformational change necessary for RhoA activation and full Cell Spreading.
Yuguang Xiong - One of the best experts on this subject based on the ideXlab platform.
-
Membrane Feedback Controls Signaling Regulation of Cell Spreading
Biophysical Journal, 2011Co-Authors: Padmini Rangamani, Michael P. Sheetz, Marc-antoine Fardin, Olivier Rossier, Yuguang Xiong, Azi Lipshtat, Ravi IyengarAbstract:Cell motility and Spreading are regulated by signaling from the integrin receptors. Interaction between the integrin receptors and substrates such as fibronectin triggers the activation of downstream signaling pathways, resulting in the activation of actin regulating proteins such as Arp2/3, gelsolin and profilin. We have developed an integrated model of Cell Spreading regulated by integrin signaling network to understand the role of signaling during fast isotropic Spreading, when fibroblasts spread on fibronectin coated slides. The three dimensional stochastic Spreading model was developed using differential geometry techniques and is coupled with a deterministic model for integrin signaling regulation. We find that Cell Spreading is a robust process and depends on signaling only for the initiation of Spreading but not for maintaining the Spreading dynamics. Our model further predicts that signaling dynamics in the absence of Cdc42 and WASP reduce the Spreading rate to a small extent but do not affect the shape evolution of the Spreading Cell. These predictions were verified by experiments conducted with dominant negative Cdc42 Cells and wiskostatin effects on Cell Spreading. Computational analyses predicted that the Spreading shape evolution is controlled by the physical properties of the plasma membrane such as membrane surface load and membrane bending ridigity. Simulations from our model identified that changing these properties affects the Spreading dynamics, in particular the shape evolution. In contrast, changing information flow through the Cell signaling network has little effect. Overall isotropic fast Spreading of fibroblasts on fibronectin-coated surfaces depends strongly on the biophysical properties of the plasma membrane and is robust to changes in the signaling dynamics.
-
A three-dimensional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D) that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.
-
A Three dimesional stochastic spatio-temporal model of Cell Spreading
Nature Precedings, 2007Co-Authors: Yuguang Xiong, Padmini Rangamani, Benjamin Dubin-thaler, Michael Sheetz, Ravi IyengarAbstract:Cell motility is important for many physiological processes and the underlyingbiochemical reactions motility have been well-characterized. Mathematical models, usingthe biochemical reactions and focused on different types of Spreading behavior have beenconstructed and analyzed. In this study, we build on these previous models to develop athree-dimensional stochastic model of isotropic Spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic Cell Spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic Spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic Spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D)that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the Cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic Cell Spreading.