Effect of Nanoparticle Surface Charge at the Plasma Membrane and Beyond

Herein, we demonstrate that the surface charge of gold nanoparticles (AuNPs) plays a critical role in modulating membrane potential of different malignant and nonmalignant cell types and subsequent downstream intracellular events. The findings presented here describe a novel mechanism for cell-nanoparticle interactions and AuNP uptake: modulation of membrane potential and its effect on intracellular events. These studies will help understand the biology of cell-nanoparticle interactions and facilitate the engineering of nanoparticles for specific intracellular targets

Ca²⁺-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

<p>Abstract</p> <p>Background</p> <p>Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca²⁺-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards T_H2-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca²⁺-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma.</p> <p>Methods</p> <p>Lung slices of 100 to 200 μm thickness were obtained from T-bet KO- and wild-type mice. Airway contraction in response to acetylcholine (ACH) was measured by video-microscopy and Ca²⁺-signaling in single ASMC of lung slices was assessed using two-photon-microscopy.</p> <p>Results</p> <p>Airways from T-bet KO-mice showed increased baseline airway tone (BAT) and BHR compared to wild-type mice. This could be mimicked by incubation of lung slices from wild-type mice with IL-13. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca²⁺-concentrations, whereas BHR correlated with higher ACH-induced Ca²⁺-transients and an increased proportion of ASMC showing Ca²⁺-oscillations. Emptying intracellular Ca²⁺-stores using caffeine or cyclopiazonic acid induced higher Ca²⁺-elevations in ASMC from T-bet KO- compared to wild-type mice.</p> <p>Conclusion</p> <p>Altered Ca²⁺-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO-mice as a murine asthma model. We propose that a higher Ca²⁺-content of the intracellular Ca²⁺-stores is involved in the pathophysiology of these changes.</p