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Full-Text Articles in Engineering
Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.
Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.
Chemical and Biochemical Engineering Faculty Research & Creative Works
Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 …
Superelastic And Ph-Responsive Degradable Dendrimer Cryogels Prepared By Cryo-Aza-Michael Addition Reaction, Juan Wang, Hu Yang
Superelastic And Ph-Responsive Degradable Dendrimer Cryogels Prepared By Cryo-Aza-Michael Addition Reaction, Juan Wang, Hu Yang
Chemical and Biochemical Engineering Faculty Research & Creative Works
Dendrimers exhibit super atomistic features by virtue of their well-defined discrete quantized nanoscale structures. Here, we show that hyperbranched amine-terminated polyamidoamine (PAMAM) dendrimer G4.0 reacts with linear polyethylene glycol (PEG) diacrylate (575 g/mol) via the aza-Michael addition reaction at a subzero temperature (-20 °C), namely cryo-aza-Michael addition, to form a macroporous superelastic network, i.e., dendrimer cryogel. Dendrimer cryogels exhibit biologically relevant Young's modulus, high compression elasticity and super resilience at ambient temperature. Furthermore, the dendrimer cryogels exhibit excellent rebound performance and do not show significant stress relaxation under cyclic deformation over a wide temperature range (-80 to 100 °C). The …
Optimal Aggregation Of Fcεri With A Structurally Defined Trivalent Ligand Overrides Negative Regulation Driven By Phosphatases, Avanika Mahajan, Dipak Barua, Patrick Cutler, Diane S. Lidke, Flor A. Espinoza, Carolyn Pehlke, Rachel Grattan, Yuko Kawakami, Chang-Shung Tung, Andrew R. M. Bradbury, William S. Hlavacek, Bridget S. Wilson
Optimal Aggregation Of Fcεri With A Structurally Defined Trivalent Ligand Overrides Negative Regulation Driven By Phosphatases, Avanika Mahajan, Dipak Barua, Patrick Cutler, Diane S. Lidke, Flor A. Espinoza, Carolyn Pehlke, Rachel Grattan, Yuko Kawakami, Chang-Shung Tung, Andrew R. M. Bradbury, William S. Hlavacek, Bridget S. Wilson
Chemical and Biochemical Engineering Faculty Research & Creative Works
To investigate why responses of mast cells to antigen-induced IgE receptor (FcεRI) aggregation depend nonlinearly on antigen dose, we characterized a new artificial ligand, DF3, through complementary modeling and experimentation. This ligand is a stable trimer of peptides derived from bacteriophage T4 fibritin, each conjugated to a hapten (DNP). We found low and high doses of DF3 at which degranulation of mast cells sensitized with DNP-specific IgE is minimal, but ligand-induced receptor aggregation is comparable to aggregation at an intermediate dose, optimal for degranulation. This finding makes DF3 an ideal reagent for studying the balance of negative and positive signaling …
Recruitment Of The Adaptor Protein Grb2 To Egfr Tetramers, Noga Kozer, Dipak Barua, Christine Henderson, Eduoard C. Nice, Antony W. Burgess, William S. Hlavacek, Andrew H. A. Clayton
Recruitment Of The Adaptor Protein Grb2 To Egfr Tetramers, Noga Kozer, Dipak Barua, Christine Henderson, Eduoard C. Nice, Antony W. Burgess, William S. Hlavacek, Andrew H. A. Clayton
Chemical and Biochemical Engineering Faculty Research & Creative Works
Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades. Here, we investigated how recruitment of Grb2 to EGFR is affected by the spatial organization and quaternary state of activated EGFR. We used the techniques of image correlation spectroscopy (ICS) and lifetime-detected Förster resonance energy transfer (also known as FLIM-based FRET or FLIM-FRET) to measure ligand-induced receptor clustering and Grb2 binding to activated EGFR in BaF/3 cells. BaF/3 cells were stably transfected with fluorescently labeled forms of Grb2 (Grb2-mRFP) and EGFR (EGFR-eGFP). Following stimulation of the cells with …
Modeling The Effect Of Apc Truncation On Destruction Complex Function In Colorectal Cancer Cells, Dipak Barua, William S. Hlavacek
Modeling The Effect Of Apc Truncation On Destruction Complex Function In Colorectal Cancer Cells, Dipak Barua, William S. Hlavacek
Chemical and Biochemical Engineering Faculty Research & Creative Works
In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β-catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β-catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK-3β, which are recruited by Axin, mediate phosphorylation of β-catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β-catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a …
Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh
Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh
Chemical and Biochemical Engineering Faculty Research & Creative Works
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. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry …
Computational Models Of Tandem Src Homology 2 Domain Interactions And Application To Phosphoinositide 3-Kinase, Dipak Barua, James R. Faeder, Jason M. Haugh
Computational Models Of Tandem Src Homology 2 Domain Interactions And Application To Phosphoinositide 3-Kinase, Dipak Barua, James R. Faeder, Jason M. Haugh
Chemical and Biochemical Engineering Faculty Research & Creative Works
Intracellular signal transduction proteins typically utilize multiple interaction domains for proper targeting, and thus a broad diversity of distinct signaling complexes may be assembled. Considering the coordination of only two such domains, as in tandem Src homology 2 (SH2) domain constructs, gives rise to a kinetic scheme that is not adequately described by simple models used routinely to interpret in vitro binding measurements. To analyze the interactions between tandem SH2 domains and bisphosphorylated peptides, we formulated detailed kinetic models and applied them to the phosphoinositide 3-kinase p85 regulatory subunit/platelet-derived growth factor β-receptor system. Data for this system from different in …