Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects.

Dysregulation of extracellular signal-regulated kinases (ERK1/2) is linked to several diseases including heart failure, genetic syndromes and cancer. Inhibition of ERK1/2, however, can cause severe cardiac side-effects, precluding its wide therapeutic application. ERKT188-autophosphorylation was identified to cause pathological cardiac hypertrophy. Here we report that interference with ERK-dimerization, a prerequisite for ERKT188-phosphorylation, minimizes cardiac hypertrophy without inducing cardiac adverse effects: an ERK-dimerization inhibitory peptide (EDI) prevents ERKT188-phosphorylation, nuclear ERK1/2-signaling and cardiomyocyte hypertrophy, protecting from pressure-overload-induced heart failure in mice whilst preserving ERK1/2-activity and cytosolic survival signaling. We also examine this alternative ERK1/2-targeting strategy in cancer: indeed, ERKT188-phosphorylation is strongly upregulated in cancer and EDI efficiently suppresses cancer cell proliferation without causing cardiotoxicity. This powerful cardio-safe strategy of interfering with ERK-dimerization thus combats pathological ERK1/2-signaling in heart and cancer, and may potentially expand therapeutic options for ERK1/2-related diseases, such as heart failure and genetic syndromes.

Gradient metal nanoislands as a unified surface enhanced Raman scattering and surface enhanced infrared absorption platform for analytics.

In the last few decades, the use of plasmonics in vibrational spectroscopy has expanded the scope of (bio)analytical investigations. Nevertheless, there is a demand for a combined platform that can be simultaneously efficient for Surface Enhanced Raman Scattering (SERS) and Surface Enhanced Infrared Absorption (SEIRA). Here, we present a solution on the basis of a plasmonic Ag nanoparticle layer with a thickness gradient. The optical resonance along the layer varies from the visible to the infrared range offering optimal and intermediate sites for SERS and SEIRA of the analyte molecule (mercaptobenzonitrile). Enhancement factors for the same mode were determined to be ca. 104 and 170 for SERS and SEIRA, respectively. We present a full optical and vibrational characterization and demonstrate further tunability. The platform resolves reproducibility and comparability issues by a combination of the two methods. It also offers individualized solutions for different investigation conditions, i.e. a choice between excitation wavelengths and resonant Raman molecules. The multiple applicabilities of the presented unifying substrate can contribute to the expansion of the vibrational spectroscopic field and to analytics.

Polarization-Dependent Atomic Force Microscopy-Infrared Spectroscopy (AFM-IR): Infrared Nanopolarimetric Analysis of Structure and Anisotropy of Thin Films and Surfaces.

Infrared techniques enable nondestructive and label-free studies of thin films with high chemical and structural contrast. In this work, we review recent progress and perspectives in the nanoscale analysis of anisotropic materials using an extended version of the atomic force microscopy-infrared (AFM-IR) technique. This advanced photothermal technique, includes polarization control of the incoming light and bridges the gap in IR spectroscopic analysis of local anisotropic material properties. Such local anisotropy occurs in a wide range of materials during molecular nucleation, aggregation, and crystallization processes. However, analysis of the anisotropy in morphology and structure can be experimentally and theoretically demanding as it is related to order and disorder processes in ranges from nanoscopic to macroscopic length scales, depending on preparation and environmental conditions. In this context IR techniques can significantly assist as IR spectra can be interpreted in the framework of optical models and numerical calculations with respect to both, the present chemical conditions as well as the micro- and nanostructure. With these extraordinary analytic possibilities, the advanced AFM-IR approach is an essential puzzle piece in direction to connect nanoscale and macroscale anisotropic thin film properties experimentally. In this review, we highlight the analytic possibilities of AFM-IR for studies on nanoscale anisotropy with a set of examples for polymer, plasmonic, and polaritonic films, as well as aggregates of large molecules and proteins.

Functionalization of any substrate using covalently modified large area CVD graphene.

We report a novel route for the functionalization of any substrates, including chemically inert substrates. CVD grown graphene is electrochemically functionalized with p-(N-maleimido)phenyl residues and consecutively transferred to various substrates. The transfer process is shown to be without noticeable loss. The functional layer exhibits a thickness of appx. 4.5 nm.

Supramolecular Orientation in Anisotropic Assemblies by Infrared Nanopolarimetry.

We report on the experimental characterization of anisotropic supramolecular assemblies by infrared (IR) nanopolarimetry. The presented IR absorption anisotropy imaging method simultaneously provides nanoscale-resolved insights into internal composition, intermolecular interactions, and supramolecular orientation in a label-free and noninvasive fashion. Our study of porphyrin aggregates demonstrates that their morphology can be correlated with stable J-type and metastable H-type stacking-induced anisotropic organization, revealing different oriented attachment growth mechanisms supported by theory. This analysis establishes the broad applicability of IR nanopolarimetric studies to supramolecular polymerization and biomolecular assemblies, opening up new routes in polymer science and macromolecular research.

Gyrotropy in achiral materials: the coupled oscillator model.

A coupled oscillator model is developed to explain the observation of gyrotropy in achiral metamaterials. By the action of distinct excitation modes, which only combine under oblique incidence, the measurement of circular birefringence in a split-ring resonator (SRR) array is explained. The symmetry of the SRR resembles the water molecule, and parallels between the systems are drawn.