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Vascular Biotransport Considerations in Signaling Cascades

Abstract

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

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