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A cell-based sensor of fluid shear stress for microfluidics.

ABSTRACT: Microsystems designed for cell-based studies or applications inherently require fluid handling. Flows within such systems inevitably generate fluid shear stress (FSS) that may adversely affect cell health. Simple assays of cell viability, morphology or growth are typically reported to indicate any gross disturbances to cell physiology. However, no straightforward metric exists to specifically evaluate physiological implications of FSS within microfluidic devices, or among competing microfluidic technologies. This paper presents the first genetically encoded cell sensors that fluoresce in a quantitative fashion upon FSS pathway activation. We picked a widely used cell line (NIH3T3s) and created a transcriptional cell-sensor where fluorescence turns on when transcription of a relevant FSS-induced protein is initiated. Specifically, we chose Early Growth Factor-1 (a mechanosensitive protein) upregulation as the node for FSS detection. We verified our sensor pathway specificity and functionality by noting induced fluorescence in response to chemical induction of the FSS pathway, seen both through microscopy and flow cytometry. Importantly, we found our cell sensors to be inducible by a range of FSS intensities and durations, with a limit of detection of 2 dynes cm(-2) when applied for 30 minutes. Additionally, our cell-sensors proved their versatility by showing induction sensitivity when made to flow through an inertial microfluidic device environment with typical flow conditions. We anticipate these cell sensors to have wide application in the microsystems community, allowing the device designer to engineer systems with acceptable FSS, and enabling the end-user to evaluate the impact of FSS upon their assay of interest.

SUBMITTER: Varma S

PROVIDER: S-EPMC4443851 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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A cell-based sensor of fluid shear stress for microfluidics.

Varma Sarvesh S Voldman Joel J

Lab on a chip 20150301 6

Microsystems designed for cell-based studies or applications inherently require fluid handling. Flows within such systems inevitably generate fluid shear stress (FSS) that may adversely affect cell health. Simple assays of cell viability, morphology or growth are typically reported to indicate any gross disturbances to cell physiology. However, no straightforward metric exists to specifically evaluate physiological implications of FSS within microfluidic devices, or among competing microfluidic ...[more]

PMID: 25648195

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Project description:Blood flow produces mechanical frictional forces, parallel to the blood flow exerted on the endothelial wall of the vessel, the so-called wall shear stress (WSS). WSS sensing is associated with several vascular pathologies, but it is first a physiological phenomenon. Endothelial cell sensitivity to WSS is involved in several developmental and physiological vascular processes such as angiogenesis and vascular morphogenesis, vascular remodeling, and vascular tone. Local conditions of blood flow determine the characteristics of WSS, i.e., intensity, direction, pulsatility, sensed by the endothelial cells that, through their effect of the vascular network, impact WSS. All these processes generate a local-global retroactive loop that determines the ability of the vascular system to ensure the perfusion of the tissues. In order to account for the physiological role of WSS, the so-called shear stress set point theory has been proposed, according to which WSS sensing acts locally on vessel remodeling so that WSS is maintained close to a set point value, with local and distant effects of vascular blood flow. The aim of this article is (1) to review the existing literature on WSS sensing involvement on the behavior of endothelial cells and its short-term (vasoreactivity) and long-term (vascular morphogenesis and remodeling) effects on vascular functioning in physiological condition; (2) to present the various hypotheses about WSS sensors and analyze the conceptual background of these representations, in particular the concept of tensional prestress or biotensegrity; and (3) to analyze the relevance, explanatory value, and limitations of the WSS set point theory, that should be viewed as dynamical, and not algorithmic, processes, acting in a self-organized way. We conclude that this dynamic set point theory and the biotensegrity concept provide a relevant explanatory framework to analyze the physiological mechanisms of WSS sensing and their possible shift toward pathological situations.

Dataset Information

A cell-based sensor of fluid shear stress for microfluidics.

Publications

A cell-based sensor of fluid shear stress for microfluidics.

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