Self-Sealing of Nanoporous Low Dielectric Constant Patterns Fabricated by Nanoimprint Lithography

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58644/1/1934_ftp.pd

Modulation of ATP/ADP Concentration at the Endothelial Cell Surface by Flow: Effect of Cell Topography

Determining how flow affects the concentration of the adenine nucleotides ATP and ADP at the vascular endothelial cell (EC) surface is essential for understanding flow-induced mobilization of intracellular calcium. Previously, mathematical models were formulated to describe the ATP/ADP concentration at the EC surface; however, all previous models assumed the endothelium to be flat. In the present study we investigate the effect of surface undulations on ATP/ADP concentration at the EC surface. The results demonstrate that under certain geometric and flow conditions, the ATP + ADP concentration at the EC surface is considerably lower for a wavy cell surface than for a flat surface. Because ECs in regions of disturbed arterial flow are expected to have larger undulations than cells in non-disturbed flow zones, our findings suggest that ECs in regions of flow disturbance would exhibit lower ATP + ADP concentrations at their surfaces, which may lead to impaired calcium signaling. If validated experimentally, the present results may contribute to our understanding of endothelial cell dysfunction observed in regions of disturbed flow

Flow-Dependent Mass Transfer May Trigger Endothelial Signaling Cascades

It is well known that fluid mechanical forces directly impact endothelial signaling pathways. But while this general observation is clear, less apparent are the underlying mechanisms that initiate these critical signaling processes. This is because fluid mechanical forces can offer a direct mechanical input to possible mechanotransducers as well as alter critical mass transport characteristics (i.e., concentration gradients) of a host of chemical stimuli present in the blood stream. However, it has recently been accepted that mechanotransduction (direct mechanical force input), and not mass transfer, is the fundamental mechanism for many hemodynamic force-modulated endothelial signaling pathways and their downstream gene products. This conclusion has been largely based, indirectly, on accepted criteria that correlate signaling behavior and shear rate and shear stress, relative to changes in viscosity. However, in this work, we investigate the negative control for these criteria. Here we computationally and experimentally subject mass-transfer limited systems, independent of mechanotransduction, to the purported criteria. The results showed that the negative control (mass-transfer limited system) produced the same trends that have been used to identify mechanotransduction-dominant systems. Thus, the widely used viscosity-related shear stress and shear rate criteria are insufficient in determining mechanotransduction-dominant systems. Thus, research should continue to consider the importance of mass transfer in triggering signaling cascades

Tissue Specificity of Human Angiotensin I-Converting Enzyme.

BACKGROUND: Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. METHODS/PRINCIPAL FINDINGS: We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. CONCLUSIONS: Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs