The 67-kDa laminin receptor (67LR) is a laminin-binding protein overexpressed in various types of cancer, including bile duct carcinoma, colorectal carcinoma, cervical cancer, and breast carcinoma. 67LR plays a vital role in growth and metastasis of tumor cells and resistance to chemotherapy. Here, we show that 67LR functions as a cancer-specific death receptor. In this cell death receptor pathway, cGMP initiated cancer-specific cell death by activating the PKCδ/acid sphingomyelinase (PKCδ/ASM) pathway. Furthermore, upregulation of cGMP was a rate-determining process of 67LR-dependent cell death induced by the green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG), a natural ligand of 67LR. We found that phosphodiesterase 5 (PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and attenuated 67LR-mediated cell death. Vardenafil, a PDE5 inhibitor that is used to treat erectile dysfunction, significantly potentiated the EGCG-activated 67LR-dependent apoptosis without affecting normal cells and prolonged the survival time in a mouse xenograft model. These results suggest that PDE5 inhibitors could be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death.

Sensitive and selective biosensors for high-throughput screening are having an increasing impact in modern medical care. The establishment of robust protein biosensing platforms however remains challenging, especially when membrane proteins are involved. Although this type of proteins is of enormous relevance since they are considered in >60% of the pharmaceutical drug targets, their fragile nature (i.e., the requirement to preserve their natural lipid environment to avoid denaturation and loss of function) puts strong additional prerequisites onto a successful biochip. In this review, the leading approaches to create lipid membrane-based arrays towards the creation of membrane protein biosensing platforms are described. Liposomes assembled in micro- and nanoarrays and the successful set-ups containing functional membrane proteins, as well as the use of liposomes in networks, are discussed in the first part. Then, the complementary approaches to create cell-mimicking supported membrane patches on a substrate in an array format will be addressed. Finally, the progress in assembling free-standing (functional) lipid bilayers over nanopore arrays for ion channel sensing will be reported. This review illustrates the rapid pace by which advances are being made towards the creation of a heterogeneous biochip for the high-throughput screening of membrane proteins for diagnostics, drug screening, or drug discovery purposes.

An approach for batch preparation of liposome‐functionalized microdevices is demonstrated for remotely controlled single‐cell drug delivery. The liposome functionalized artificial bacterial flagella exhibit corkscrew swimming in 3D with micrometer positioning precision by applying an external rotating magnetic field. The devices are also capable of delivering water‐soluble drugs to single cells in vitro.

In this communication, we introduce transmembrane anion transport with pnictogen-bonding compounds and compare their characteristics with chalcogen-and halogen-bonding analogs. Tellurium-centered chalcogen bonds are at least as active as antimony-centered pnictogen bonds, whereas iodine-centered halogen bonds are three orders of magnitude less active. Irregular, voltage-dependent single-channel currents, high gating charges, efficient dye leakage and small Hill coefficients support the formation of bulky, membrane-disruptive supramolecular amphiphiles by tris(perfluorophenyl)stibanes that bind anions "too strongly." In contrast, the chalcogen-bonding bis(perfluorophenyl)tellanes do not cause leakage and excel as carriers with nanomolar activity, P(Cl/Na) = 10.4 for anion/cation selectivity and P(Cl/NO3) = 4.5 for anion selectivity. Selectivities are lower with pnictogen-bonding carriers because their membrane-disturbing 3D structure affects also weaker binders (P(Cl/Na) = 2.1, P(Cl/NO3) = 2.5). Their 2D structure, directionality, hydrophobicity and support from proximal anion-π interactions are suggested to contribute to the unique power of chalcogen bonds to transport anions across lipid bilayer membranes. The integration of unorthodox interactions into functional systems is of fundamental importance because it promises access to new activities. 1 Synthetic transport systems 2 have emerged as an attractive tool to assess the functional relevance of such interactions. Realized examples include anion-π interactions in many variations, 1 halogen bonds 3,4 and, more recently, also chalcogen bonds. 5,6 In the following, we elaborate on anion transport with pnictogen bonds in direct comparison to chalcogen and halogen bonds. These so-called s-hole interactions 7,8 originate from highly localized areas of highly positive charge density that appear on heavier and p-block elements. Associated with s* orbitals, the s holes appear at the opposite side of the covalent bonds and deepen with increasing electron deficiency of the atom. As a result, there is one s hole available per atom for halogen bonds, 9 two for chalcogen, 10 three for pnictogen 11,12 and four for tetrel bonds (Figure 1). 7,8 Increasing with polarizability, the depth of the s holes

EGCG [(−)-epigallocatechin-3-O-gallate], the major polyphenol of green tea, has cancer chemopreventive and chemotherapeutic activities. EGCG selectively inhibits cell growth and induces apoptosis in cancer cells without adversely affecting normal cells; however, the underlying molecular mechanism in vivo is unclear. In the present study, we show that EGCG-induced apoptotic activity is attributed to a lipid-raft clustering mediated through 67LR (67 kDa laminin receptor) that is significantly elevated in MM (multiple myeloma) cells relative to normal peripheral blood mononuclear cells, and that aSMase (acid sphingomyelinase) is critical for the lipid-raft clustering and the apoptotic cell death induced by EGCG. We also found that EGCG induces aSMase translocation to the plasma membrane and PKCδ (protein kinase Cδ) phosphorylation at Ser664, which was necessary for aSMase/ceramide signalling via 67LR. Additionally, orally administered EGCG activated PKCδ and aSMase in a murine MM xenograft model. These results elucidate a novel cell-death pathway triggered by EGCG for the specific killing of MM cells.

Several nanoporous platforms were functionalized with pH-responsive poly(methacrylic acid) (PMAA) brushes using surface-initiated atom transfer radical polymerization (SI-ATRP). The growth of the PMAA brush and its pH-responsive behavior from the nanoporous platforms were confirmed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). The swelling behavior of the pH-responsive PMAA brushes grafted only from the nanopore walls was investigated by AFM in aqueous liquid environment with pH values of 4 and 8. AFM images displayed open nanopores at pH 4 and closed ones at pH 8, which rationalizes their use as gating platforms. Ion conductivity across the nanopores was investigated with current-voltage measurements at various pH values. Enhanced higher resistance across the nanopores was observed in a neutral polymer brush state (lower pH values) and lower resistance when the brush was charged (higher pH values). By adding a fluorescent dye in an environment of pH 4 or pH 8 at one side of the PMAA-brush functionalized nanopore array chips, diffusion across the nanopores was followed. These experiments displayed faster diffusion rates of the fluorescent molecules at pH 4 (PMAA neutral state, open pores) and slower diffusion at pH 8 (PMAA charged state, closed pores) showing the potential of this technology toward nanoscale valve applications.

We have developed a method for electrical polarization of nuclear spins in quantum Hall systems. In a breakdown regime of odd-integer quantum Hall effect (QHE), excitation of electrons to the upper Landau subband with opposite spin polarity dynamically polarizes nuclear spins through the hyperfine interaction. The polarized nuclear spins in turn accelerate the QHE breakdown, leading to hysteretic voltage-current characteristics of the quantum Hall conductor. Control of nuclear spins in semiconductor has attracted considerable interests because nuclear spin is one of the most promising elements for implementation of quantum bit. 1 Several techniques have been developed for optical 2,3 and electrical 4,5,6,7,8,9,10,11,12 control of nuclear spins. In quantum Hall (QH) systems, two kinds of approaches for all-electrical manipulation of nuclear spins have been demonstrated. 4,5,6,7,8,9,10,11 One technique utilized spin-flip scattering of electrons between spin-resolved QH edge channels. 4,5,6,7,8 The flip of electron spin S flops nuclear spin I through the hyperfine interaction,where A is the hyperfine constant. The nuclear spin polarization was detected by measuring Hall resistance. Another technique utilized domain structure with different spin configurations in fractional QH systems. 9,10,11 The spin-flip process of electrons traveling across the domain boundary flops nuclear spins through the hyperfine interaction.Nuclear spin polarization has been also utilized as a probe to investigate electron spin properties in twodimensional electron systems (2DESs), which had not been accessed by standard magnetotransport measurements. Indeed, the excitation of spin texture in a QH system 10 and the low frequency spin fluctuations in closely separated bilayer 2DESs 13 were observed using resistively detected nuclear spin relaxation. Thus, development of a method for electrical polarization and detection of nuclear spins will open a way to find spin-dependent phenomena in QH systems.In this letter, we demonstrate a method for electrical polarization of nuclear spins using the breakdown of integer quantum Hall effect (QHE). In a breakdown regime of odd-integer QHE, electrons are excited to the upper Landau subband with opposite spin polarity. The spin-flip process of electrons dynamically polarizes nuclear spins through the hyperfine interaction. The polarized nuclear spins in turn reduce the spin-splitting energy of Landau subbands, accelerating the QHE breakdown. The voltage-current characteristic curve is shifted due to the dynamical nuclear polarization (DNP). The relevance of the DNP to the shift is confirmed by the detection of nuclear magnetic resonance (NMR).We propose a concept for electrical polarization of nu-clear spins in an odd-integer QHE regime, where the Fermi energy resides in the energy gap of spin-split Landau subbands. In this condition, the lower Landau subband (N , ↑) is fully occupied with up-spin electrons, while the higher down-spin subband (N , ↓) is empty. When a current is transmitted through the ...

The enormous progress of nanotechnology during the last decade has made it possible to fabricate a great variety of nanostructures. On the nanoscale, metals exhibit special electrical and optical properties, which can be utilized for novel applications. In particular, plasmonic sensors including both the established technique of surface plasmon resonance and more recent nanoplasmonic sensors, have recently attracted much attention. However, some of the simplest and most successful sensors, such as the glucose biosensor, are based on electrical readout. In this review we describe the implementation of electrochemistry with plasmonic nanostructures for combined electrical and optical signal transduction. We highlight results from different types of metallic nanostructures such as nanoparticles, nanowires, nanoholes or simply films of nanoscale thickness. We briefly give an overview of their optical properties and discuss implementation of electrochemical methods. In particular, we review studies on how electrochemical potentials influence the plasmon resonances in different nanostructures, as this type of fundamental understanding is necessary for successful combination of the methods. Although several combined platforms exist, many are not yet in use as sensors partly because of the complicated effects from electrochemical potentials on plasmon resonances. Yet, there are clearly promising aspects of these sensor combinations and we conclude this review by discussing the advantages of synchronized electrical and optical readout, illustrating the versatility of these technologies.