Mechanical properties are cues for many biological processes in health or disease. In the heart, changes to the extracellular matrix composition and cross-linking result in stiffening of the cellular microenvironment during development. Moreover, myocardial infarction and cardiomyopathies lead to fibrosis and a stiffer environment, affecting cardiomyocyte behavior. Here, we identify that single cardiomyocyte adhesions sense simultaneous (fast oscillating) cardiac and (slow) non-muscle myosin contractions. Together, these lead to oscillating tension on the mechanosensitive adaptor protein talin on substrates with a stiffness of healthy adult heart tissue, compared with no tension on embryonic heart stiffness and continuous stretching on fibrotic stiffness. Moreover, we show that activation of PKC leads to the induction of cardiomyocyte hypertrophy in a stiffness-dependent way, through activation of non-muscle myosin. Finally, PKC and non-muscle myosin are upregulated at the costameres in heart disease, indicating aberrant mechanosensing as a contributing factor to long-term remodeling and heart failure.
1 December 2016 in Measurement Science and Technology
Time-correlated single photon counting (TCSPC) is a widely used, robust and mature technique to measure the photon arrival time in applications such as fluorescence spectroscopy and microscopy, LIDAR and optical tomography. In the past few years there have been significant developments with wide-field TCSPC detectors, which can record the position as well as the arrival time of the photon simultaneously. In this review, we summarise different approaches used in wide-field TCSPC detection, and discuss their merits for different applications, with emphasis on fluorescence lifetime imaging.
Light–matter interactions can be strongly modified by the surrounding environment. Here, we report on the first experimental observation of molecular spontaneous emission inside a highly non-local metamaterial based on a plasmonic nanorod assembly. We show that the emission process is dominated not only by the topology of its local effective medium dispersion, but also by the non-local response of the composite, so that metamaterials with different geometric parameters but the same local effective medium properties exhibit different Purcell factors. A record-high enhancement of a decay rate is observed, in agreement with the developed quantitative description of the Purcell effect in a non-local medium. An engineered material non-locality introduces an additional degree of freedom into quantum electrodynamics, enabling new applications in quantum information processing, photochemistry, imaging and sensing with macroscopic composites.