Functionalization of quantum dots (QDs) with a single biomolecular tag using traditional approaches in bulk solution has met with limited success. DNA polyhedra consist of an internal void bounded by a well-defined three-dimensional structured surface. The void can house cargo and the surface can be functionalized with stoichiometric and spatial precision. Here, we show that monofunctionalized QDs can be achieved by encapsulating QDs inside DNA icosahedra and functionalizing the DNA shell with an endocytic ligand. We deployed the DNA-encapsulated QDs for real time imaging of three different endocytic ligands - folic acid, galectin-3 (Gal3) and the Shiga toxin B-subunit (STxB). Single particle tracking of Gal3 or STxB-functionalized, QD-loaded DNA icosahedra allows us to monitor compartmental dynamics along endocytic pathways. These DNA-encapsulated QDs that bear a unique stoichiometry of endocytic ligands represent a new class of molecular probes for quantitative imaging of endocytic receptor dynamics.
Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell–deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell–deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non–B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell–deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell–deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.
Recently, a new class of smectic liquid crystal phases (SmCP phases) characterized by the spontaneous formation of macroscopic chiral domains from achiral bent-core molecules has been discovered. We have carried out Monte Carlo simulations of a minimal hard spherocylinder dimer model to investigate the role of excluded volume interations in determining the phase behavior of bent-core materials and to probe the molecular origins of polar and chiral symmetry breaking. We present the phase diagram as a function of pressure or density and dimer opening angle ψ. With decreasing ψ, a transition from a nonpolar to a polar smectic phase is observed near ψ = 167• , and the nematic phase becomes thermodynamically unstable for ψ < 135• . No chiral smectic or biaxial nematic phases were found. [5]. In all of these examples, chirality is an intrinsic property built into the chemical structure of the LC molecules. Recently, a new class of smectic LC phases (SmCP phases) characterized by the spontaneous formation of macroscopic chiral layers from achiral molecules has been discovered [6,7]. The molecules comprising these phases have 'bow' or 'banana' shaped cores. The resulting phases exhibit two spontaneous symmetry-breaking instabilities: polar molecular orientational ordering within the layer plane, and molecular tilt, which together produce chiral layers with a handedness that depends on the direction of the tilt relative to the polar axis. Very large second order nonlinear optical (NLO) coefficients have been measured in the ferroelectric state of such materials, bearing some promising applications in NLO devices [8,9].From a theoretical point of view, the relationship of phase behavior to the specific bent-core molecular shape is of fundamental interest. In this paper, we investigate a minimal excluded volume model of bent-core mesogens, focusing on the molecular origin of polar and/or chiral symmetry breaking. Of particular interest is the coupling between polar and chiral symmetry breaking. In all bentcore materials studied to date, polar symmetry breaking is accompanied by chiral symmetry breaking induced by molecular tilt. This empirical fact raises the question whether there is a fundamental connection between polarity and chirality in molecular fluids. Another empirical observation is that bent-core materials exhibiting SmCP phases generally do not exhibit nematic phases, although two exceptions have recently been reported [10,11]. One objective of this study is to establish the molecular shape requirements for the occurence of the nematic phase in bent-core materials. Finally, we explore the possibility of biaxial nematic ordering in bent-core materials, motivated by recent experimental indications [11,12].Hard core models are particularly appealing due to their simplicity and relative ease of computation, both in simulation and theory. In particular, hard spherocylinders have been widely studied as simple models for conventional LCs [13,14]. This model exhibits rich phase behavior including isotropic, nematic, s...
Active biological processes like transcription, replication, recombination, DNA repair, and DNA packaging encounter bent DNA. Machineries associated with these processes interact with the DNA at short length (<100 base pair) scale. Thus, the study of elasticity of DNA at such length scale is very important. We use fully atomistic molecular dynamics (MD) simulations along with various theoretical methods to determine elastic properties of dsDNA of different lengths and base sequences. We also study DNA elasticity in nucleosome core particle (NCP) both in the presence and the absence of salt. We determine stretch modulus and persistence length of short dsDNA and nucleosomal DNA from contour length distribution and bend angle distribution, respectively. For short dsDNA, we find that stretch modulus increases with ionic strength while persistence length decreases. Calculated values of stretch modulus and persistence length for DNA are in quantitative agreement with available experimental data. The trend is opposite for NCP DNA. We find that the presence of histone core makes the DNA stiffer and thus making the persistence length 3-4 times higher than the bare DNA. Similarly, we also find an increase in the stretch modulus for the NCP DNA. Our study for the first time reports the elastic properties of DNA when it is wrapped around the histone core in NCP. We further show that the WLC model is inadequate to describe DNA elasticity at short length scale. Our results provide a deeper understanding of DNA mechanics and the methods are applicable to most protein-DNA complexes.
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