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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2012)

The vasculature of our body sensitively responds to varied biomolecules. These biomolecules are critical in triggering downstream protein synthesis, mRNA transcription, and DNA synthesis, and hence vascular homeostasis. We take these studies as an opportunity to understand the orchestra of (1) charge properties, (2) mechanical topography, (3) fluid dynamics, and (4) molecular cues to obtain a systemic and integrative understanding of the vasculature. In this work, we introduce a novel in-situ streaming potential device to quantify the electrostatic contribution of morphological changes in confluent endothelial cells (ECs). We further study the effect of mechanical topographies of nan-patterned titanium on ECs. Both species mass transfer and mechanotransduction have been suggested as the underlying mechanisms for activating ECs. However, in recent years, the dominance of mechanotransduction at the endothelium has been qualitatively demonstrated through in-vitro experiments attempting to emulate the vasculature. Thus, it remains plausible that biomolecular mass transfer may be significant in vascular signaling pathways. This work shows that a more cautious analysis that delineates endothelial mechanotransduction from mass transfer remains warranted. Having said that, we propose a novel, in-vitro experimental methodology using membrane separations technology. The methodology is flexible and robust, in that it can be used with mass transfer-limited and reaction-limited processes and can address a number of controllable scenarios. Finally, we characterize the endothelial behavior in healthy and diseased ECs by characterizing the sub-endothelium and the underlying endothelial signaling pathways. The work presented here demonstrates the vast number of biotransport factors to be captured while studying the fascinating vascular endothelium. Understanding the mechanistic factors of ECs and the triggered signaling pathways is crucial to our search for novel therapeutics.

Keywords - vaculature, charge, mechanical, mass transfer, mechanotransduction, signaling

    Cover page: Vascular Biotransport Considerations in Signaling Cascades
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2014)
    In this work, we evaluate the in vitro response of endothelial cells (EC) to variation in precisely-defined, micrometer to sub-micrometer scale topography on two different substrate materials, titanium (Ti) and silicon (Si). Both substrates possess identically-patterned surfaces composed of microfabricated, groove-based gratings with groove widths ranging from 0.5 to 50 µm, grating pitch twice the groove width, and groove depth of 1.3 µm. These specific materials are chosen due to their relevance for implantable microdevice applications, while grating-based patterns are chosen for the potential they afford for inducing elongated and aligned cellular morphologies reminiscent of the native endothelium. Using EA926 cells, a human EC variant, we show significant improvement in cellular adhesion, proliferation, morphology, and function with decreasing feature size on patterned Ti substrates. Moreover, we show similar trending on patterned Si substrates, albeit to a lesser extent than on comparably patterned Ti substrates. Collectively, these results suggest promise for sub-micrometer topographic patterning in general, and sub-micrometer patterning of Ti specifically, as a means for enhancing endothelialization and neovascularisation for novel implantable microdevice applications.
      Cover page: Comparative Endothelial Cell Response on Topographically Patterned Titanium and Silicon Substrates with Micrometer to Sub-Micrometer Feature Sizes
      • Article
      • Peer Reviewed
      UC Riverside Previously Published Works (2012)
      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.
        Cover page: Flow-dependent mass transfer may trigger endothelial signaling cascades.Creative Commons 'BY-NC' version 4.0 license
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