Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was noncovalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.

The influence of a basic aqueous solution on a hydrogen-bonding-directed layer-by-layer (LbL) self-assembled film, based on poly(acrylic acid) (PAA) and poly(4-vinylpyridine) (PVP), was investigated. The composition change of a multilayer film in a NaOH solution was monitored by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and UV-vis spectroscopy. The morphology variation was observed by atomic force microscopy. A two-step variation was observed: the first step is the dissolution of PAA from the film into the basic solution; the second is the gradual reconformation of PVP polymer chains remaining on the substrate, which produces a microporous film. The evidence for the reconformation of the polymer chains was further provided by single molecule force spectroscopy. Both the release of PAA and the formation of the microporous film are attributed to the properties of the LbL film based on hydrogen bonding. This interesting and novel way to fabricate microporous films is envisaged to have potential applications in areas ranging from pharmaceutics to materials science.

How appendages, such as plant leaves or animal limbs, develop asymmetric shapes remains a fundamental question in biology. Although ongoing research has revealed the genetic regulation of organ pattern formation, how gene activity ultimately directs organ shape remains unclear. Here, we show that leaf dorsoventral (adaxial-abaxial) polarity signals lead to mechanical heterogeneity of the cell wall, related to the methyl-esterification of cell-wall pectins in tomato and Arabidopsis. Numerical simulations predicate that mechanical heterogeneity is sufficient to produce the asymmetry seen in planar leaves. Experimental tests that alter pectin methyl-esterification, and therefore cell wall mechanical properties, support this model and lead to polar changes in gene expression, suggesting the existence of a feedback mechanism for mechanical signals in morphogenesis. Thus, mechanical heterogeneity within tissue may underlie organ shape asymmetry.

Bacterial spores possess a series of concentrically arranged protective structures that contribute to dormancy, survival and, ultimately, germination. One of these structures, the coat, is present in all spores. In Bacillus anthracis, however, the spore is surrounded by an additional, poorly understood, morphologically complex structure called the exosporium. Here, we characterize three previously discovered exosporium proteins called ExsFA (also known as BxpB), ExsFB (a highly related paralogue of exsFA/bxpB) and IunH (similar to an inosine-uridine-preferring nucleoside hydrolase). We show that in the absence of ExsFA/BxpB, the exosporium protein BclA accumulates asymmetrically to the forespore pole closest to the midpoint of the sporangium (i.e. the mother-cell-proximal pole of the forespore), instead of uniformly encircling the exosporium. ExsFA/BxpB may also have a role in coat assembly, as mutant spore surfaces lack ridges seen in wild-type spores and have a bumpy appearance. ExsFA/BxpB also has a modest but readily detected effect on germination. Nonetheless, an exsFA/bxpB mutant strain is fully virulent in both intramuscular and aerosol challenge models in Guinea pigs. We show that the pattern of localization of ExsFA/BxpB-GFP is a ring, consistent with a location for this protein in the basal layer of the exosporium. In contrast, ExsFB-GFP fluorescence is a solid oval, suggesting a distinct subcellular location for ExsFB-GFP. We also used these fusion proteins to monitor changes in the subcellular locations of these proteins during sporulation. Early in sporulation, both fusions were present throughout the mother cell cytoplasm. As sporulation progressed, GFP fluorescence moved from the mother cell cytoplasm to the forespore surface and formed either a ring of fluorescence, in the case of ExsFA/BxpB, or a solid oval of fluorescence, in the case of ExsFB. IunH-GFP also resulted in a solid oval of fluorescence. We suggest the interpretation that at least some ExsFB-GFP and IunH-GFP resides in the region between the coat and the exosporium, called the interspace. INTRODUCTIONThe bacilli and clostridia encompass a large number of species that produce highly resistant dormant cells, called spores, in response to stress (Fritze, 2004;Nicholson, 2002). Prominent among these species is Bacillus anthracis, which has played a central historical role in our understanding of the transmission of disease and the mechanisms of toxin action, and which has reemerged as a serious threat to human life in light of its utility as a biological weapon (Alibek, 1999;Koch, 1876;Mock & Fouet, 2001). Because the B. anthracis spore is the infectious particle for the disease anthrax, a deeper understanding of spore composition, assembly and function could be very useful in combating this threat.Abbreviations: AFM, atomic force microscopy; IFM, immunofluorescence microscopy; IM, intramuscular; TEM, thin-section electron microscopy.A supplementary table listing PCR primers used in this study is available with the online version of thi...

Semiconductor-based surface enhanced Raman scattering (SERS) has attracted great attention due to its excellent spectral reproducibility, high uniformity, and good anti-interference ability. However, its relatively low SERS sensitivity still hinders its further developments in both performance and applications. Since the SERS is a peculiar surface effect, investigating the facet-dependent SERS activity of semiconductor nanostructures is crucial to boost their SERS signals. Although the semiconductor facet-dependent SERS effect is predicted via numerical calculations, convincing experimental evidence is scarce due to complicated and undefined surface conditions. In this work, three facet-defined ({100}, {110}, and {111} facets) Cu O microcrystals (MCs) with clear surface atomic configuration are utilized to investigate the facet-dependent SERS effect. The results from the Kelvin probe force microscopy measurements on single Cu O polyhedron, demonstrate that the facet-dependent work function plays a crucial role in the interfacial charge transfer process. Comparing with the {110} and {111} facets, the {100} facet possesses the lowest electronic work function, which enables more efficient interfacial charge transfer. The simulation results further confirm that the {100}-facets can transfer the most electrons from Cu O MCs to molecules due to its lowest facet work function, resulting in the largest increment of the molecular polarization.

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The fabrication of stable polyelectrolyte/Au nanoparticle multilayer films was achieved by the UV irradiation of layer‐by‐layer self‐assembled multilayers consisting of diazoresins and Au nanoparticles. The method promises to be a simple and efficient strategy to construct covalently attached organic/inorganic multilayer hybrids.

Fibrillar collagens form the structural basis of organs and tissues including the vasculature, bone, and tendon. They are also dynamic, organizational scaffolds that present binding and recognition sites for ligands, cells, and platelets. We interpret recently published X-ray diffraction findings and use atomic force microscopy data to illustrate the significance of new insights into the functional organization of the collagen fibril. These data indicate that collagen’s most crucial functional domains localize primarily to the overlap region, comprising a constellation of sites we call the ‘master control region’. Moreover, collagens most exposed aspect contains its most stable part - the C-terminal region that controls collagen assembly, cross-linking, and blood clotting. Hidden beneath the fibril surface exists a constellation of ‘cryptic’ sequences poised to promote hemostasis and cell-collagen interactions in tissue injury and regeneration. These findings begin to address several important, and previously unresolved, questions: How functional domains are organized in the fibril, which domains are accessible, and which require proteolysis or structural trauma to become exposed. Here we speculate as to how collagen fibrillar organization impacts molecular processes relating to tissue growth, development, and repair.