TRPV4 Regulates the Macrophage Metabolic Response to Limit Sepsis-induced Lung Injury.

Sepsis is a systemic inflammatory response that requires effective macrophage metabolic functions to resolve ongoing inflammation. Previous work showed that the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), mediates macrophage phagocytosis and cytokine production in response to lung infection. Here, we show that TRPV4 regulates glycolysis in a stiffness-dependent manner by augmenting macrophage glucose uptake by GLUT1. In addition, TRPV4 is required for LPS-induced phagolysosome maturation in a GLUT1-dependent manner. In a cecal slurry mouse model of sepsis, TRPV4 regulates sepsis-induced glycolysis as measured by BAL fluid (BALF) lactate and sepsis-induced lung injury as measured by BALF total protein and lung compliance. TRPV4 is necessary for bacterial clearance in the peritoneum to limit sepsis-induced lung injury. It is interesting that BALF lactate is increased in patients with sepsis compared with healthy control participants, supporting the relevance of lung cell glycolysis to human sepsis. These data show that macrophage TRPV4 is required for glucose uptake through GLUT1 for effective phagolysosome maturation to limit sepsis-induced lung injury. Our work presents TRPV4 as a potential target to protect the lung from injury in sepsis.

Controlling Gold Morphology Using Electrodeposition for the Preparation of Electrochemical Aptamer-Based Sensors.

Nanostructuring of gold surfaces to enhance electroactive surface area has proven to significantly enhance the performance of electrochemical aptamer-based (E-AB) sensors, particularly for electrodes on the microscale. Unlike for sensors fabricated on polished gold surfaces, predicting the behavior of E-AB sensors on surfaces with varied gold morphologies becomes more intricate due to the effects of surface roughness and the shapes and sizes of surface features on supporting a self-assembled monolayer. In this study, we explored the impact of gold morphology characteristics on sensor performance, evaluating parameters such as signal change in response to the addition of the target analyte, aptamer probe packing density, and continuous sensing ability. Our findings reveal that surface area enhancement can either enhance or diminish sensor performance for gold nanostructured E-AB sensors, contingent upon the surface morphology. In particular, our results indicate that the aptamer packing density and target analyte signal change results are heavily dependent on gold nanostructure size and features. Sensing surfaces with larger nanoparticle diameters, which were prepared using electrodeposition at a constant potential, had a reduced aptamer packing density and exhibited diminished sensor performance. However, the equivalent packing density of polished electrodes did not yield the equivalent signal change. Other surfaces that were prepared using pulsed waveform electrodeposition achieved optimal signal change with a deposition time, tdep, of 120 s, and increased deposition time with enhanced electroactive surface area resulted in minimized signal changes and more rapid sensor degradation. By investigating sensing surfaces with varied morphologies, we have demonstrated that enhancing the electroactive surface does not always enhance the signal change of the sensor, and aptamer packing density alone does not dictate observed signal change trends. We anticipate that understanding how electrodeposition techniques enhance or diminish sensor performance will pave the way for further exploration of nanostructure-aptamer relationships, contributing to the future development of optimized, miniaturized electrochemical aptamer-based sensors for continuous, in vivo sensing.