Department of Chemical and Biomolecular Engineering
Open Access Policy Deposits (484)
Graphite-Supported Pt n Cluster Electrocatalysts: Major Change of Active Sites as a Function of the Applied Potential
The oxygen reduction reaction (ORR) plays a key role in renewable energy transformation processes. Unfortunately, it is inherently sluggish, which greatly limits its industrial application. Sub-nano-cluster-decorated electrode interfaces are promising candidate ORR electrocatalysts. However, understanding the nature of the active sites on these catalysts under electrocatalytic conditions presents a formidable challenge for both experiment and theory, due to their dynamic fluxional character. Here, we combine global optimization with the electronic Grand Canonical DFT to elucidate the structure and dynamics of subnano Ptnclusters deposited on electrified graphite. We show that, under electrochemical conditions, these clusters exist as statistical ensembles of multiple states, whose fluxionality is greatly affected by the applied potential, electrolyte, and adsorbate coverage. The results reveal the presence of potential-dependent active sites and, hence, reaction energetics.
Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo
Background
A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions.Methodology and principal findings
We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells.Conclusion
Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies.Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells
VEGF can be secreted in multiple isoforms with variable affinity for extracellular proteins and different abilities to induce vascular morphogenesis, but the molecular mechanisms behind these effects remain unclear. Here, we show molecular distinctions between signaling initiated from soluble versus matrix-bound VEGF, which mediates a sustained level of VEGFR2 internalization and clustering. Exposure of endothelial cells to matrix-bound VEGF elicits prolonged activation of VEGFR2 with differential phosphorylation of Y1214, and extended activation kinetics of p38. These events require association of VEGFR2 with beta1 integrins. Matrix-bound VEGF also promotes reciprocal responses on beta1 integrin by inducing its association with focal adhesions; a response that is absent upon exposure to soluble VEGF. Inactivation of beta1 integrin blocks the prolonged phosphorylation of Y1214 and consequent activation of p38. Combined, these results indicate that when in the context of extracellular matrix, activation of VEGFR2 is distinct from that of soluble VEGF in terms of recruitment of receptor partners, phosphorylation kinetics, and activation of downstream effectors.