Integration of Chemo-mechanical signaling in response to fluid shear stress by the endothelium.

Physical forces exert profound effects on cells affecting fate, function, and response to stressors. In the case of the endothelium, the layer that resides in the inner surface of blood vessels, the collective effect of hemodynamic forces influences the onset and severity of vascular pathologies. Justifiably, much emphasis has been placed in understanding how endothelial cells sense and respond to mechanical challenges, particularly hemodynamic shear stress. In this review, we highlight recent developments that have expanded our understanding of the molecular mechanisms underlying mechanotransduction. We describe examples of protein compartmentalization in response to shear stress, consider the contribution of the glycocalyx, and discuss the specific role ion channels in response to flow. We also highlight the recently recognized contribution of the receptor ALK5 in sensing turbulent flow. Research in the last three years has enriched our understanding of the molecular landscape responsible for recognizing and transducing shear stress responses, including novel transcriptional-dependent and transcriptional-independent mechanisms.

A Luminescent Manganese PhotoCORM for CO Delivery to Cellular Targets under the Control of Visible Light.

A photoactive manganese carbonyl complex derived from dansylimidazole (Imdansyl), namely, [Mn(Imdansyl)(CO)3(phen)](CF3SO3) (1), has been synthesized and structurally characterized. This is the first luminescent manganese carbonyl-based photoCORM reported in the literature. This complex exhibits CO release under the exclusive control of low-power broadband visible light. The corresponding rhenium carbonyl complex, namely, [Re(Imdansyl)(CO)3(phen)](CF3SO3) (2), has also been reported, which is luminescent but sensitive only to UV-B (λ<315 nm) light. The entry of the manganese photoCORM into the human colorectal adenocarcinoma cells (HT-29) has been demonstrated with the aid of fluorescence microscopy. Irradiation of the photoCORM-loaded cancer cells to visible light leads to a dose-dependent apoptotic cell death.