Cortical cell stiffness is independent of substrate mechanics.

Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This 'soft substrate effect' leads to an underestimation of a cell's elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a 'composite cell-substrate model'. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes

Flexible and ultra-lightweight polymer membrane lasers

The authors acknowledge financial support from the European Research Council (ERC StG ABLASE, 640012), the Scottish Funding Council (via SUPA) and EPSRC (EP/P030017/1). M.K. and J.M.E.G. acknowledge funding from the EPSRC DTG (EP/M506631/1 and EP/L505079/1). M.S. acknowledges funding from the European Commission for a Marie Sklodowska-Curie Individual Fellowship (659213). I.D.W.S. acknowledges funding from a Royal Society Wolfson research merit award.Organic semiconductors enable the fabrication of a range of lightweight and mechanically flexible optoelectronic devices. Most organic semiconductor lasers, however, have remained rigid until now, predominantly due to the need for a support substrate. Here, we use a simple fabrication process to make membrane-based, substrate-less and extremely thin (< 500 nm) organic distributed feedback lasers that offer ultralow-weight (m/A <0.5 gm−2) and excellent mechanical flexibility. We show operation of the lasers as free-standing membranes and transfer them onto other substrates, e.g. a banknote, where the unique lasing spectrum is readily read out and used as security feature. The pump thresholds and emission intensity of our membrane lasers are well within the permissible exposures for ocular safety and we demonstrate integration on contact lenses as wearable security tags.Publisher PDFPeer reviewe

Long-term imaging of cellular forces with high precision by elastic resonator interference stress microscopy

This project has received funding from the Human Frontiers Science Program (RGY0074/2013), the Scottish Funding Council (via SUPA), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 640012), the EPSRC DTP (EP/L505079/1), the RS MacDonald Charitable Trust and the MRC (G1100116 and G110312/1).Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to data analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell–substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic resonator interference stress microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity). This enables investigation of minute vertical stresses (<1 Pa) involved in podosome protrusion, protein-specific cell–substrate interaction and amoeboid migration through spatial confinement in real time. ERISM requires no zero-force reference and avoids phototoxic effects, which facilitates force monitoring over multiple days and at high frame rates and eliminates the need to detach cells after measurements. This allows observation of slow processes such as differentiation and further investigation of cells, for example, by immunostaining.PostprintPeer reviewe

Monolithic Integration of Multi-Color Organic LEDs by Grayscale Lithography

A single step process to fabricate arrays of organic LEDs with emission colors across the entire visible spectrum is introduced. This multi-color monolithic integration of OLEDs is enabled by a grayscale lithography scheme that inscribes thickness profiles into crosslinkable hole-transport layers. When introduced into a micro-cavity OLED, these thickness variations translate into shifts of the resonant wavelength of the cavity

NIR-Absorbing Merocyanine Dyes for BHJ Solar Cells

We have synthesized a series of new, polymethine chain extended merocyanine dyes 1-4 bearing varied acceptor units and an aminothiophene donor moiety. The optical and electronic properties of these new merocyanines have been studied in comparison with their corresponding lower homologues 5-8, which contain two methine groups less, by UV-vis and electro-optical absorption (EOA) spectroscopy and cyclic voltammetry. The absorption spectra of pi-extended merocyanines are markedly red-shifted, and their extinction coefficients are significantly increased compared to those of their lower homologues. The photovoltaic characteristics of these dyes have been explored in devices using them as donor and PC61BM fullerene as acceptor materials. Our detailed studies reveal that, despite more favorable absorption properties, the it-extended merocyanines exhibit lower short-circuit current densities (J(SC)) as well as decreased open-circuit voltages (V-OC) and power conversion efficiencies (PCE) compared with those of their respective lower homologues. The unexpected decreased J(SC) values could be explained in terms of looser packing features of pi-extended chromophores in the solid state as revealed by single-crystal X-ray analysis of two pairs (1/S and 4/8) of these dyes. By optimization of device setup PCE of 2.3% has been achieved with the Jr-extended donor material 4

Simple, Highly Efficient Vacuum-Processed Bulk Heterojunction Solar Cells Based on Merocyanine Dyes

In order to be competitive on the energy market, organic solar cells with higher efficiency are needed. To date, polymer solar cells have retained the lead with efficiencies of up to 8%. However, research on small molecule solar cells has been catching up throughout recent years and is showing similar efficiencies, however, only for more sophisticated multilayer device configurations. In this work, a simple, highly efficient, vacuum-processed small molecule solar cell based on merocyanine dyes - traditional colorants that can easily be mass-produced and purified - is presented. In the past, merocyanines have been successfully introduced in solution-processed as well as vacuum-processed devices, demonstrating efficiencies up to 4.9%. Here, further optimization of devices is achieved while keeping the same simple layer stack, ultimately leading to efficiencies beyond the 6% mark. In addition, physical properties such as the charge carrier transport and the cell performance under various light intensities are addressed

Real-time imaging of cellular forces using optical interference

Important dynamic processes in mechanobiology remain elusive due to a lack of tools to image the small cellular forces at play with sufficient speed and throughput. Here, we introduce a fast, interference-based force imaging method that uses the illumination of an elastic deformable microcavity with two rapidly alternating wavelengths to map forces. We show real-time acquisition and processing of data, obtain images of mechanical activity while scanning across a cell culture, and investigate sub-second fluctuations of the piconewton forces exerted by macrophage podosomes. We also demonstrate force imaging of beating neonatal cardiomyocytes at 100 fps which reveals mechanical aspects of spontaneous oscillatory contraction waves in between the main contraction cycles. These examples illustrate the wider potential of our technique for monitoring cellular forces with high throughput and excellent temporal resolution. Studying dynamic processes in mechanobiology has been challenging due to lack of appropriate tools. Here, the authors present an interference-based method, illuminated via two rapidly alternating wavelengths, which enables real-time mapping of nanoscale forces with sub-second mechanical fluctuations

Cell force-driven basement membrane disruption fuels EGF- and stiffness-induced invasive cell dissemination from benign breast gland acini

Local basement membrane (BM) disruption marks the initial step of breast cancer invasion. The activation mechanisms of force-driven BM-weakening remain elusive. We studied the mechanical response of MCF10A-derived human breast cell acini with BMs of tuneable maturation to physical and soluble tumour-like extracellular matrix (ECM) cues. Traction force microscopy (TFM) and elastic resonator interference stress microscopy (ERISM) were used to quantify pro-invasive BM stress and protrusive forces. Substrate stiffening and mechanically impaired BM scaffolds induced the invasive transition of benign acini synergistically. Robust BM scaffolds attenuated this invasive response. Additional oncogenic EGFR activation compromised the BMs’ barrier function, fuelling invasion speed and incidence. Mechanistically, EGFR-PI3-Kinase downstream signalling modulated both MMP- and force-driven BM-weakening processes. We show that breast acini form non-proteolytic and BM-piercing filopodia for continuous matrix mechanosensation, which significantly push and pull on the BM and ECM under pro-invasive conditions. Invasion-triggered acini further shear and compress their BM by contractility-based stresses that were significantly increased (3.7-fold) compared to non-invasive conditions. Overall, the highest amplitudes of protrusive and contractile forces accompanied the highest invasiveness. This work provides a mechanistic concept for tumour ECM-induced mechanically misbalanced breast glands fuelling force-driven BM disruption. Finally, this could facilitate early cell dissemination from pre-invasive lesions to metastasize eventually