Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform
Abstract
Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. In this paper, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry and optical imaging. The device seamlessly integrates cell culture, stimulation, and preparation with downstream measurements permitting hands-free, automated analysis to minimize experimental variability. The platform was used to interrogate IgE receptor (FcεRI) signaling, which is responsible for triggering allergic reactions, in RBL-2H3 cells. Following on-chip crosslinking of IgE-FcεRI complexes by multivalent antigen, we monitored signaling events including protein phosphorylation, calcium mobilization and the release of inflammatory mediators. The results demonstrate the ability of our platform to produce quantitative measurements on a cell-by-cell basis from just a few hundred cells. Finally, model-based analysis of the Syk phosphorylation data suggestsmore »
- Authors:
-
- Sandia National Lab. (SNL-CA), Livermore, CA (United States). Biotechnology and Bioengineering Dept.
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group. Theoretical Division. Center for Nonlinear Studies
- Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Pathology. Cancer Center
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE; National Inst. of Health (NIH) (United States)
- Contributing Org.:
- Univ. of New Mexico, Albuquerque, NM (United States)
- OSTI Identifier:
- 1321718
- Report Number(s):
- LA-UR-12-23884
Journal ID: ISSN 1932-6203
- Grant/Contract Number:
- AC52-06NA25396; AC04-94AL85000; P50GM085273
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 3; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; biological science; phosphorylation; microfluidics; cytokines; protein kinase signaling cascade; flow cytometry; cell degranulation; fluorescence imaging; enzyme-linked immunoassays
Citation Formats
Liu, Yanli, Barua, Dipak, Liu, Peng, Wilson, Bridget S., Oliver, Janet M., Hlavacek, William S., and Singh, Anup K. Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform. United States: N. p., 2013.
Web. doi:10.1371/journal.pone.0060159.
Liu, Yanli, Barua, Dipak, Liu, Peng, Wilson, Bridget S., Oliver, Janet M., Hlavacek, William S., & Singh, Anup K. Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform. United States. https://doi.org/10.1371/journal.pone.0060159
Liu, Yanli, Barua, Dipak, Liu, Peng, Wilson, Bridget S., Oliver, Janet M., Hlavacek, William S., and Singh, Anup K. Wed .
"Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform". United States. https://doi.org/10.1371/journal.pone.0060159. https://www.osti.gov/servlets/purl/1321718.
@article{osti_1321718,
title = {Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform},
author = {Liu, Yanli and Barua, Dipak and Liu, Peng and Wilson, Bridget S. and Oliver, Janet M. and Hlavacek, William S. and Singh, Anup K.},
abstractNote = {Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. In this paper, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry and optical imaging. The device seamlessly integrates cell culture, stimulation, and preparation with downstream measurements permitting hands-free, automated analysis to minimize experimental variability. The platform was used to interrogate IgE receptor (FcεRI) signaling, which is responsible for triggering allergic reactions, in RBL-2H3 cells. Following on-chip crosslinking of IgE-FcεRI complexes by multivalent antigen, we monitored signaling events including protein phosphorylation, calcium mobilization and the release of inflammatory mediators. The results demonstrate the ability of our platform to produce quantitative measurements on a cell-by-cell basis from just a few hundred cells. Finally, model-based analysis of the Syk phosphorylation data suggests that heterogeneity in Syk phosphorylation can be attributed to protein copy number variations, with the level of Syk phosphorylation being particularly sensitive to the copy number of Lyn.},
doi = {10.1371/journal.pone.0060159},
journal = {PLoS ONE},
number = 3,
volume = 8,
place = {United States},
year = {Wed Mar 27 00:00:00 EDT 2013},
month = {Wed Mar 27 00:00:00 EDT 2013}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 21 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Single-cell protein analysis
journal, February 2012
- Wu, Meiye; Singh, Anup K.
- Current Opinion in Biotechnology, Vol. 23, Issue 1, p. 83-88
Achieving Stability of Lipopolysaccharide-Induced NF- B Activation
journal, September 2005
- Covert, M. W.
- Science, Vol. 309, Issue 5742
Oscillations in NF- B Signaling Control the Dynamics of Gene Expression
journal, October 2004
- Nelson, D. E.
- Science, Vol. 306, Issue 5696
The ups and downs of p53: understanding protein dynamics in single cells
journal, April 2009
- Batchelor, Eric; Loewer, Alexander; Lahav, Galit
- Nature Reviews Cancer, Vol. 9, Issue 5
Separating intrinsic from extrinsic fluctuations in dynamic biological systems
journal, July 2011
- Hilfinger, A.; Paulsson, J.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 29
Dynamic Single-Cell Analysis for Quantitative Biology
journal, December 2006
- Carlo, Dino Di; Lee, Luke P.
- Analytical Chemistry, Vol. 78, Issue 23
Fully Integrated Microfluidic Platform Enabling Automated Phosphoprofiling of Macrophage Response
journal, May 2009
- Srivastava, Nimisha; Brennan, James S.; Renzi, Ronald F.
- Analytical Chemistry, Vol. 81, Issue 9, p. 3261-3269
Single-cell NF-κB dynamics reveal digital activation and analogue information processing
journal, June 2010
- Tay, Savaş; Hughey, Jacob J.; Lee, Timothy K.
- Nature, Vol. 466, Issue 7303
Microfluidic devices for measuring gene network dynamics in single cells
journal, August 2009
- Bennett, Matthew R.; Hasty, Jeff
- Nature Reviews Genetics, Vol. 10, Issue 9
A microfluidic chemostat for experiments with bacterial and yeast cells
journal, August 2005
- Groisman, Alex; Lobo, Caroline; Cho, HoJung
- Nature Methods, Vol. 2, Issue 9
Microfluidic application-specific integrated device for monitoring direct cell-cell communication via gap junctions between individual cell pairs
journal, May 2005
- Lee, Philip J.; Hung, Paul J.; Shaw, Robin
- Applied Physics Letters, Vol. 86, Issue 22
Analytical tools for characterizing heterogeneity in organelle content
journal, August 2012
- Anand, Robbyn K.; Chiu, Daniel T.
- Current Opinion in Chemical Biology, Vol. 16, Issue 3-4
Versatile, Fully Automated, Microfluidic Cell Culture System
journal, November 2007
- Gómez-Sjöberg, Rafael; Leyrat, Anne A.; Pirone, Dana M.
- Analytical Chemistry, Vol. 79, Issue 22
Microfluidic fluorescence in situ hybridization and flow cytometry (μFlowFISH)
journal, January 2011
- Liu, Peng; Meagher, Robert J.; Light, Yooli K.
- Lab on a Chip, Vol. 11, Issue 16, p. 2673-2679
Isotropically etched radial micropore for cell concentration, immobilization, and picodroplet generation
journal, January 2009
- Perroud, Thomas D.; Meagher, Robert J.; Kanouff, Michael P.
- Lab on a Chip, Vol. 9, Issue 4, p. 507-515
Microfluidically-unified cell culture, sample preparation, imaging and flow cytometry for measurement of cell signaling pathways with single cell resolution
journal, January 2012
- Wu, Meiye; Perroud, Thomas D.; Srivastava, Nimisha
- Lab on a Chip, Vol. 12, Issue 16, p. 2823-2831
Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data
journal, February 2007
- Bischoff, Stephan C.
- Nature Reviews Immunology, Vol. 7, Issue 2
IgE in allergy and asthma today
journal, March 2008
- Gould, Hannah J.; Sutton, Brian J.
- Nature Reviews Immunology, Vol. 8, Issue 3
Small, Mobile FcɛRI Receptor Aggregates Are Signaling Competent
journal, September 2009
- Andrews, Nicholas L.; Pfeiffer, Janet R.; Martinez, A. Marina
- Immunity, Vol. 31, Issue 3
Kinematics of Specifically Captured Circulating Tumor Cells in Bio-Functionalized Microchannels
journal, August 2010
- Cheung, Luthur Siu-Lun; Zheng, Xiangjun; Wang, Lian
- Journal of Microelectromechanical Systems, Vol. 19, Issue 4
Critical stresses for cancer cell detachment in microchannels
journal, July 2009
- Couzon, Cécile; Duperray, Alain; Verdier, Claude
- European Biophysics Journal, Vol. 38, Issue 8
Controlling the selection stringency of phage display using a microfluidic device
journal, January 2009
- Liu, Yanli; Adams, Jonathan D.; Turner, Kelisha
- Lab on a Chip, Vol. 9, Issue 8
Selection of phage-displayed peptides on live adherent cells in microfluidic channels
journal, April 2011
- Wang, J.; Liu, Y.; Teesalu, T.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 17
Stochasticity in gene expression: from theories to phenotypes
journal, May 2005
- Kærn, Mads; Elston, Timothy C.; Blake, William J.
- Nature Reviews Genetics, Vol. 6, Issue 6
Investigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model
journal, April 2003
- Faeder, James R.; Hlavacek, William S.; Reischl, Ilona
- The Journal of Immunology, Vol. 170, Issue 7
BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
journal, June 2004
- Blinov, M. L.; Faeder, J. R.; Goldstein, B.
- Bioinformatics, Vol. 20, Issue 17
Shuttling of initiating kinase between discrete aggregates of the high affinity receptor for IgE regulates the cellular response
journal, February 1997
- Torigoe, C.; Goldstein, B.; Wofsy, C.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 4
A Computational Model for Early Events in B Cell Antigen Receptor Signaling: Analysis of the Roles of Lyn and Fyn
journal, June 2012
- Barua, Dipak; Hlavacek, William S.; Lipniacki, Tomasz
- The Journal of Immunology, Vol. 189, Issue 2
Integrated signalling pathways for mast-cell activation
journal, February 2006
- Gilfillan, Alasdair M.; Tkaczyk, Christine
- Nature Reviews Immunology, Vol. 6, Issue 3
Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis
journal, April 2012
- Gaudet, Suzanne; Spencer, Sabrina L.; Chen, William W.
- PLoS Computational Biology, Vol. 8, Issue 4
The versatility and universality of calcium signalling
journal, October 2000
- Berridge, Michael J.; Lipp, Peter; Bootman, Martin D.
- Nature Reviews Molecular Cell Biology, Vol. 1, Issue 1
Roles for Ca2+ stores release and two Ca2+ influx pathways in the Fc epsilon R1-activated Ca2+ responses of RBL-2H3 mast cells.
journal, July 1995
- Lee, R. J.; Oliver, J. M.
- Molecular Biology of the Cell, Vol. 6, Issue 7
Imaging asynchronous changes in intracellular Ca2+ in individual stimulated tumor mast cells.
journal, March 1988
- Millard, P. J.; Gross, D.; Webb, W. W.
- Proceedings of the National Academy of Sciences, Vol. 85, Issue 6
In situ measurement of degranulation as a biosensor based on RBL-2H3 mast cells
journal, November 2004
- Naal, Rose Mary Z. G.; Tabb, Joel; Holowka, David
- Biosensors and Bioelectronics, Vol. 20, Issue 4
Impaired secretion and increased insolubilization of IgE-receptor complexes in mycophenolic acid-treated (guanine nucleotide-depleted) RBL-2H3 mast cells
journal, December 1991
- Wilson, Bridget Smith; Seagrave, Jeanclare; Oliver, Janet M.
- Journal of Cellular Physiology, Vol. 149, Issue 3
Cytokine production by mast cells and basophils
journal, December 1991
- Galli, Stephen J.; Gordon, John R.; Wershil, Barry K.
- Current Opinion in Immunology, Vol. 3, Issue 6
TNF alpha is important in human lung allergic reactions.
journal, July 1996
- Casale, T. B.; Costa, J. J.; Galli, S. J.
- American Journal of Respiratory Cell and Molecular Biology, Vol. 15, Issue 1
Positive and Negative Regulation of Mast Cell Activation by Lyn via the FcεRI
journal, November 2005
- Xiao, Wenbin; Nishimoto, Hajime; Hong, Hong
- The Journal of Immunology, Vol. 175, Issue 10
Increased Expression of Genes Linked to FcεRI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells
journal, December 2005
- Hernandez-Hansen, Valerie; Bard, Julie D. J.; Tarleton, Christy A.
- The Journal of Immunology, Vol. 175, Issue 12
Redundant and Opposing Functions of Two Tyrosine Kinases, Btk and Lyn, in Mast Cell Activation
journal, August 2000
- Kawakami, Yuko; Kitaura, Jiro; Satterthwaite, Anne B.
- The Journal of Immunology, Vol. 165, Issue 3
MAST CELLS AS “TUNABLE” EFFECTOR AND IMMUNOREGULATORY CELLS: Recent Advances
journal, April 2005
- Galli, Stephen J.; Kalesnikoff, Janet; Grimbaldeston, Michele A.
- Annual Review of Immunology, Vol. 23, Issue 1
Monophosphorylation of CD79a and CD79b ITAM Motifs Initiates a SHIP-1 Phosphatase-Mediated Inhibitory Signaling Cascade Required for B Cell Anergy
journal, November 2011
- O'Neill, Shannon K.; Getahun, Andrew; Gauld, Stephen B.
- Immunity, Vol. 35, Issue 5
Molecular regulation of mast cell activation
journal, June 2006
- Rivera, J.; Gilfillan, A.
- Journal of Allergy and Clinical Immunology, Vol. 117, Issue 6
Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells
journal, June 2003
- Gonzalez-Espinosa, Claudia; Odom, Sandra; Olivera, Ana
- The Journal of Experimental Medicine, Vol. 197, Issue 11
Syk and Lyn mediate distinct Syk phosphorylation events in FcɛRI-signal transduction: Implications for regulation of IgE-mediated degranulation
journal, November 2010
- Sanderson, Michael P.; Wex, Eva; Kono, Takeshi
- Molecular Immunology, Vol. 48, Issue 1-3
Syk and pTyr'd: Signaling through the B cell antigen receptor
journal, July 2009
- Geahlen, Robert L.
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1793, Issue 7
Microfluidic-Based Cell Sorting of Francisella tularensis Infected Macrophages Using Optical Forces
journal, August 2008
- Perroud, Thomas D.; Kaiser, Julia N.; Sy, Jay C.
- Analytical Chemistry, Vol. 80, Issue 16, p. 6365-6372
Formation of a Mast Cell Synapse: FcεRI Membrane Dynamics upon Binding Mobile or Immobilized Ligands on Surfaces
journal, December 2009
- Carroll-Portillo, Amanda; Spendier, Kathrin; Pfeiffer, Janet
- The Journal of Immunology, Vol. 184, Issue 3
Log-normal Distributions across the Sciences: Keys and Clues
journal, January 2001
- Limpert, Eckhard; Stahel, Werner A.; Abbt, Markus
- BioScience, Vol. 51, Issue 5
Stochastic Simulation of Chemical Kinetics
journal, May 2007
- Gillespie, Daniel T.
- Annual Review of Physical Chemistry, Vol. 58, Issue 1
Cytokine production by mast cells and basophils
journal, February 1992
- Galli, Stephen J.; Gordon, John R.; K. Wershil, Barry
- Current Biology, Vol. 2, Issue 2
Impaired secretion and increased insolubilization of IgE-receptor complexes in mycophenolic acid-treated (guanine nucleotide-depleted) RBL-2H3 mast cells
journal, December 1991
- Wilson, Bridget Smith; Seagrave, Jeanclare; Oliver, Janet M.
- Journal of Cellular Physiology, Vol. 149, Issue 3
Critical stresses for cancer cell detachment in microchannels
journal, July 2009
- Couzon, Cécile; Duperray, Alain; Verdier, Claude
- European Biophysics Journal, Vol. 38, Issue 8
Protein-tyrosine phosphorylation: an essential component of FcεRI signaling
journal, January 1992
- Benhamou, Marc; Siraganian, Reuben P.
- Immunology Today, Vol. 13, Issue 6
Syk and pTyr'd: Signaling through the B cell antigen receptor
journal, July 2009
- Geahlen, Robert L.
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1793, Issue 7
In situ measurement of degranulation as a biosensor based on RBL-2H3 mast cells
journal, November 2004
- Naal, Rose Mary Z. G.; Tabb, Joel; Holowka, David
- Biosensors and Bioelectronics, Vol. 20, Issue 4
Analytical tools for characterizing heterogeneity in organelle content
journal, August 2012
- Anand, Robbyn K.; Chiu, Daniel T.
- Current Opinion in Chemical Biology, Vol. 16, Issue 3-4
Single-cell protein analysis
journal, February 2012
- Wu, Meiye; Singh, Anup K.
- Current Opinion in Biotechnology, Vol. 23, Issue 1, p. 83-88
Small, Mobile FcɛRI Receptor Aggregates Are Signaling Competent
journal, September 2009
- Andrews, Nicholas L.; Pfeiffer, Janet R.; Martinez, A. Marina
- Immunity, Vol. 31, Issue 3
Monophosphorylation of CD79a and CD79b ITAM Motifs Initiates a SHIP-1 Phosphatase-Mediated Inhibitory Signaling Cascade Required for B Cell Anergy
journal, November 2011
- O'Neill, Shannon K.; Getahun, Andrew; Gauld, Stephen B.
- Immunity, Vol. 35, Issue 5
Molecular regulation of mast cell activation
journal, June 2006
- Rivera, J.; Gilfillan, A.
- Journal of Allergy and Clinical Immunology, Vol. 117, Issue 6
Syk and Lyn mediate distinct Syk phosphorylation events in FcɛRI-signal transduction: Implications for regulation of IgE-mediated degranulation
journal, November 2010
- Sanderson, Michael P.; Wex, Eva; Kono, Takeshi
- Molecular Immunology, Vol. 48, Issue 1-3
Dynamic Single-Cell Analysis for Quantitative Biology
journal, December 2006
- Carlo, Dino Di; Lee, Luke P.
- Analytical Chemistry, Vol. 78, Issue 23
Microfluidic-Based Cell Sorting of Francisella tularensis Infected Macrophages Using Optical Forces
journal, August 2008
- Perroud, Thomas D.; Kaiser, Julia N.; Sy, Jay C.
- Analytical Chemistry, Vol. 80, Issue 16, p. 6365-6372
Fully Integrated Microfluidic Platform Enabling Automated Phosphoprofiling of Macrophage Response
journal, May 2009
- Srivastava, Nimisha; Brennan, James S.; Renzi, Ronald F.
- Analytical Chemistry, Vol. 81, Issue 9, p. 3261-3269
The versatility and universality of calcium signalling
journal, October 2000
- Berridge, Michael J.; Lipp, Peter; Bootman, Martin D.
- Nature Reviews Molecular Cell Biology, Vol. 1, Issue 1
The ups and downs of p53: understanding protein dynamics in single cells
journal, April 2009
- Batchelor, Eric; Loewer, Alexander; Lahav, Galit
- Nature Reviews Cancer, Vol. 9, Issue 5
Stochasticity in gene expression: from theories to phenotypes
journal, May 2005
- Kærn, Mads; Elston, Timothy C.; Blake, William J.
- Nature Reviews Genetics, Vol. 6, Issue 6
Integrated signalling pathways for mast-cell activation
journal, February 2006
- Gilfillan, Alasdair M.; Tkaczyk, Christine
- Nature Reviews Immunology, Vol. 6, Issue 3
Isotropically etched radial micropore for cell concentration, immobilization, and picodroplet generation
journal, January 2009
- Perroud, Thomas D.; Meagher, Robert J.; Kanouff, Michael P.
- Lab on a Chip, Vol. 9, Issue 4, p. 507-515
Controlling the selection stringency of phage display using a microfluidic device
journal, January 2009
- Liu, Yanli; Adams, Jonathan D.; Turner, Kelisha
- Lab on a Chip, Vol. 9, Issue 8
Microfluidically-unified cell culture, sample preparation, imaging and flow cytometry for measurement of cell signaling pathways with single cell resolution
journal, January 2012
- Wu, Meiye; Perroud, Thomas D.; Srivastava, Nimisha
- Lab on a Chip, Vol. 12, Issue 16, p. 2823-2831
Selection of phage-displayed peptides on live adherent cells in microfluidic channels
journal, April 2011
- Wang, J.; Liu, Y.; Teesalu, T.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 17
Separating intrinsic from extrinsic fluctuations in dynamic biological systems
journal, July 2011
- Hilfinger, A.; Paulsson, J.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 29
Imaging asynchronous changes in intracellular Ca2+ in individual stimulated tumor mast cells.
journal, March 1988
- Millard, P. J.; Gross, D.; Webb, W. W.
- Proceedings of the National Academy of Sciences, Vol. 85, Issue 6
Shuttling of initiating kinase between discrete aggregates of the high affinity receptor for IgE regulates the cellular response
journal, February 1997
- Torigoe, C.; Goldstein, B.; Wofsy, C.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 4
Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells
journal, June 2003
- Gonzalez-Espinosa, Claudia; Odom, Sandra; Olivera, Ana
- The Journal of Experimental Medicine, Vol. 197, Issue 11
Roles for Ca2+ stores release and two Ca2+ influx pathways in the Fc epsilon R1-activated Ca2+ responses of RBL-2H3 mast cells.
journal, July 1995
- Lee, R. J.; Oliver, J. M.
- Molecular Biology of the Cell, Vol. 6, Issue 7
BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
journal, June 2004
- Blinov, M. L.; Faeder, J. R.; Goldstein, B.
- Bioinformatics, Vol. 20, Issue 17
Oscillations in NF- B Signaling Control the Dynamics of Gene Expression
journal, October 2004
- Nelson, D. E.
- Science, Vol. 306, Issue 5696
Achieving Stability of Lipopolysaccharide-Induced NF- B Activation
journal, September 2005
- Covert, M. W.
- Science, Vol. 309, Issue 5742
A Noisy Paracrine Signal Determines the Cellular NF-κB Response to Lipopolysaccharide
journal, October 2009
- Lee, Timothy K.; Denny, Elissa M.; Sanghvi, Jayodita C.
- Science Signaling, Vol. 2, Issue 93
TNF alpha is important in human lung allergic reactions.
journal, July 1996
- Casale, T. B.; Costa, J. J.; Galli, S. J.
- American Journal of Respiratory Cell and Molecular Biology, Vol. 15, Issue 1
Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis
journal, April 2012
- Gaudet, Suzanne; Spencer, Sabrina L.; Chen, William W.
- PLoS Computational Biology, Vol. 8, Issue 4
A Computational Model for Early Events in B Cell Antigen Receptor Signaling: Analysis of the Roles of Lyn and Fyn
journal, June 2012
- Barua, Dipak; Hlavacek, William S.; Lipniacki, Tomasz
- The Journal of Immunology, Vol. 189, Issue 2
Theory of Equilibrium Binding of Symmetric Bivalent Haptens to Cell Surface Antibody: Application to Histamine Release from Basophils
journal, July 1978
- Dembo, Micah; Goldstein, Byron
- The Journal of Immunology, Vol. 121, Issue 1
Exploiting the difference between intrinsic and extrinsic kinases: implications for regulation of signaling by immunoreceptors.
journal, December 1997
- Wofsy, C.; Torigoe, C.; Kent, U. M.
- The Journal of Immunology, Vol. 159, Issue 12
Redundant and Opposing Functions of Two Tyrosine Kinases, Btk and Lyn, in Mast Cell Activation
journal, August 2000
- Kawakami, Yuko; Kitaura, Jiro; Satterthwaite, Anne B.
- The Journal of Immunology, Vol. 165, Issue 3
Investigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model
journal, April 2003
- Faeder, James R.; Hlavacek, William S.; Reischl, Ilona
- The Journal of Immunology, Vol. 170, Issue 7
Works referencing / citing this record:
Microfluidic Platforms for Single-Cell Protein Analysis
journal, December 2013
- Liu, Yanli; Singh, Anup K.
- Journal of Laboratory Automation, Vol. 18, Issue 6, p. 446-454
Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor
journal, January 2019
- Erickson, Keesha E.; Rukhlenko, Oleksii S.; Shahinuzzaman, Md
- PLOS Computational Biology, Vol. 15, Issue 1
Timescale Separation of Positive and Negative Signaling Creates History-Dependent Responses to IgE Receptor Stimulation
journal, November 2017
- Harmon, Brooke; Chylek, Lily A.; Liu, Yanli
- Scientific Reports, Vol. 7, Issue 1