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Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells.

ABSTRACT: The objective of this study is to develop a device to mimic a microfluidic system of human arterial blood vessels. The device combines fluid shear stress (FSS) and cyclic stretch (CS), which are resulting from blood flow and blood pressure, respectively. The device can reveal real-time observation of dynamic morphological change of cells in different flow fields (continuous flow, reciprocating flow and pulsatile flow) and stretch. We observe the effects of FSS and CS on endothelial cells (ECs), including ECs align their cytoskeleton proteins with the fluid flow direction and paxillin redistribution to the cell periphery or the end of stress fibers. Thus, understanding the morphological and functional changes of endothelial cells on physical stimuli can help us to prevent and improve the treatment of cardiovascular diseases.

SUBMITTER: Chu PY

PROVIDER: S-EPMC10251125 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells.

Chu Pei-Yu PY Hsieh Han-Yun HY Chung Pei-Shan PS Wang Pai-Wen PW Wu Ming-Chung MC Chen Yin-Quan YQ Kuo Jean-Cheng JC Fan Yu-Jui YJ

iScience 20230519 6

The objective of this study is to develop a device to mimic a microfluidic system of human arterial blood vessels. The device combines fluid shear stress (FSS) and cyclic stretch (CS), which are resulting from blood flow and blood pressure, respectively. The device can reveal real-time observation of dynamic morphological change of cells in different flow fields (continuous flow, reciprocating flow and pulsatile flow) and stretch. We observe the effects of FSS and CS on endothelial cells (ECs), ...[more]

PMID: 37305698

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Project description:Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology. Therefore, the effects of hemodynamic stresses that arise due to bifurcating vessel geometries on ECs are not well understood. Here, we introduce and characterize a microfluidic model that mimics both the flow conditions and the endothelial/extracellular matrix (ECM) architecture of bifurcating blood vessels to systematically monitor changes in endothelial permeability mediated by the local flow dynamics at specific locations along the bifurcating vessel structure. We show that bifurcated fluid flow (BFF) that arises only at the base of a vessel bifurcation and is characterized by stagnation pressure of ?38 dyn cm-2 and approximately zero shear stress induces significant decrease in EC permeability compared to the static control condition in a nitric oxide (NO)-dependent manner. Similarly, intravascular laminar shear stress (LSS) (3 dyn cm-2) oriented tangential to ECs located downstream of the vessel bifurcation also causes a significant decrease in permeability compared to the static control condition via the NO pathway. In contrast, co-application of transvascular flow (TVF) (?1 ?m s-1) with BFF and LSS rescues vessel permeability to the level of the static control condition, which suggests that TVF has a competing role against the stabilization effects of BFF and LSS. These findings introduce BFF at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics control vascular function in vivo.

Dataset Information

Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells.

Publications

Development of vessel mimicking microfluidic device for studying mechano-response of endothelial cells.

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