Dataset Information

Controlling the Kinetics of Self-Reproducing Micelles by Catalyst Compartmentalization in a Biphasic System.

ABSTRACT: Compartmentalization of reactions is ubiquitous in biochemistry. Self-reproducing lipids are widely studied as chemical models of compartmentalized biological systems. Here, we explore the effect of catalyst location on copper-catalyzed azide-alkyne cycloadditions which drive the self-reproduction of micelles from phase-separated components. Tuning the hydrophilicity of the copper-ligand complex, so that hydro-phobic or -philic catalysts are used in combination with hydro-philic and -phobic coupling partners, provides a wide range of reactivity patterns. Analysis of the kinetic data shows that reactions with a hydrophobic catalyst are faster than with a hydrophilic catalyst. Diffusion-ordered spectroscopy experiments suggest compartmentalization of the hydrophobic catalyst inside micelles while the hydrophilic catalyst remains in the bulk aqueous phase. The autocatalytic effects observed can be tuned by varying reactant structure and coupling a hydrophilic alkyne and hydrophobic azide results in a more pronounced autocatalytic effect. We propose and test a model that rationalizes the observations in terms of the phase behavior of the reaction components and catalysts.

SUBMITTER: Post EAJ

PROVIDER: S-EPMC6459585 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Controlling the Kinetics of Self-Reproducing Micelles by Catalyst Compartmentalization in a Biphasic System.

Post Elias A J EAJ Fletcher Stephen P SP

The Journal of organic chemistry 20190212 5

Compartmentalization of reactions is ubiquitous in biochemistry. Self-reproducing lipids are widely studied as chemical models of compartmentalized biological systems. Here, we explore the effect of catalyst location on copper-catalyzed azide-alkyne cycloadditions which drive the self-reproduction of micelles from phase-separated components. Tuning the hydrophilicity of the copper-ligand complex, so that hydro-phobic or -philic catalysts are used in combination with hydro-philic and -phobic coup ...[more]

PMID: 30698970

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Project description:BackgroundIn analogy to normal stem cell differentiation, the current cancer stem cell (CSC) model presumes a hierarchical organization and an irreversible differentiation in tumor tissue. Accordingly, CSCs should comprise only a small subset of the tumor cells, which feeds tumor growth. However, some recent findings raised doubts on the general applicability of the CSC model and asked for its refinement.Methodology/principal findingsIn this study we analyzed the CSC properties of mammary carcinoma cells derived from transgenic (WAP-T) mice. We established a highly tumorigenic WAP-T cell line (G-2 cells) that displays stem-like traits. G-2 cells, as well as their clonal derivates, are closely related to primary tumors regarding histology and gene expression profiles, and reflect heterogeneity regarding their differentiation states. G-2 cultures comprise cell populations in distinct differentiation states identified by co-expression of cytoskeletal proteins (cytokeratins and vimentin), a combination of cell surface markers and a set of transcription factors. Cellular subsets sorted according to expression of CD24a, CD49f, CD61, Epcam, Sca1, and Thy1 cell surface proteins, or metabolic markers (e.g. ALDH activity) are competent to reconstitute the initial cellular composition. Repopulation efficiency greatly varies between individual subsets and is influenced by interactions with the respective complementary G-2 cellular subset. The balance between differentiation states is regulated in part by the transcription factor Sox10, as depletion of Sox10 led to up-regulation of Twist2 and increased the proportion of Thy1-expressing cells representing cells in a self-renewable, reversible, quasi-mesenchymal differentiation state.Conclusions/significanceG-2 cells constitute a self-reproducing cancer cell system, maintained by bi- and unidirectional conversion of complementary cellular subsets. Our work contributes to the current controversial discussion on the existence and nature of CSC and provides a basis for the incorporation of alternative hypotheses into the CSC model.

Dataset Information

Controlling the Kinetics of Self-Reproducing Micelles by Catalyst Compartmentalization in a Biphasic System.

Publications

Controlling the Kinetics of Self-Reproducing Micelles by Catalyst Compartmentalization in a Biphasic System.

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