Facile fabrication of stable wettability gradients on elastomeric surfaces for applications in water collection and controlled cell adhesion.

We have developed a simple and effective method to prepare stable wettability gradients on an elastomeric soft substrate, polydimethylsiloxane (PDMS). In our method, a partially cured PDMS film composed of a definite ratio of elastomer and crosslinking agent was heated over a hot surface with a temperature gradient. This causes differential thermal curing of the PDMS film and the water contact angle (wettability) of the resultant surface showed gradual variation across the length. This method allows us to design and fabricate wettability gradients with rationally controlled directionality and shapes (e.g., linear and radial gradients). The stability of the wettability gradients was studied and a chemical treatment method was developed to enhance the stability at room temperature. Stable wettability gradients prepared through this method can find applications as reliable platforms and scaffolds offering controlled or directional wetting and adhesion. We have demonstrated the practical applications of the wettability gradients in directional water collection, controlled crystallization of materials, and controlled cell adhesion of HeLa cells, osteoblasts and NIH/3T3 cells. The multi-functional characteristics of these wettable gradients are expected to be handy in other domains using soft materials and interfaces also.

Elevated H3K4me3 Through MLL2-WDR82 upon Hyperglycemia Causes Jagged Ligand Dependent Notch Activation to Interplay with Differentiation State of Endothelial Cells.

Endothelial-to-mesenchymal transition (EndMT) is a hallmark of diabetes-associated vascular complications. Epigenetic mechanisms emerged as one of the key pathways to regulate diabetes-associated complications. In the current study, we aimed to determine how abrupt changes in histone 3 lysine 4 tri-methylation (H3K4me3) upon hyperglycemia exposure reprograms endothelial cells to undergo EndMT. Through in vitro studies, we first establish that intermittent high-glucose exposure to EC most potently induced partial mesenchyme-like characteristics compared with transient or constant high-glucose-challenged endothelial cells. In addition, glomerular endothelial cells of BTBR Ob/Ob mice also exhibited mesenchymal-like characteristics. Intermittent hyperglycemia-dependent induction of partial mesenchyme-like phenotype of endothelial cells coincided with an increase in H3K4me3 level in both macro- and micro-vascular EC due to selective increase in MLL2 and WDR82 protein of SET1/COMPASS complex. Such an endothelial-specific heightened H3K4me3 level was also detected in intermittent high-glucose-exposed rat aorta and in kidney glomeruli of Ob/Ob mice. Elevated H3K4me3 enriched in the promoter regions of Notch ligands Jagged1 and Jagged2, thus causing abrupt expression of these ligands and concomitant activation of Notch signaling upon intermittent hyperglycemia challenge. Pharmacological inhibition and/or knockdown of MLL2 in cells in vitro or in tissues ex vivo normalized intermittent high-glucose-mediated increase in H3K4me3 level and further reversed Jagged1 and Jagged2 expression, Notch activation and further attenuated acquisition of partial mesenchyme-like phenotype of endothelial cells. In summary, the present study identifies a crucial role of histone methylation in hyperglycemia-dependent reprograming of endothelial cells to undergo mesenchymal transition and indicated that epigenetic pathways contribute to diabetes-associated vascular complications.