Abstract
ObjectiveWan et al (Proc Natl Acad Sci USA, 105, 2008, 16432) demonstrated that RBCs rapidly and transiently release a spike of 300% more ATP shortly downstream from a short microfluidic constriction where the cells experience a sudden increase in shear stress. More recent work by Cinar et al (Proc Natl Acad Sci USA, 112, 2015, 11783), however, yielded no evidence for a similar spike in ATP release downstream of the constriction. Our aim was to determine whether a transient spike in mechanotransduction is the typical response of RBCs to the sudden onset of increased shear.MethodsWe investigate ATP release downstream of a microfluidic constriction for 15 participants using a luciferase‐based photoluminescent assay.ResultsWhile we observe mechanotransductive ATP release from blood drawn from all donors, we find evidence of a spike in ATP concentration after the microfluidic constriction for only 2 of 15 participants. No clear trends in ATP release are found with respect to the magnitude of the applied shear stress, or to the gender, age, or physical activity (Baecke) index of the donor.ConclusionsIn aggregate, all data acquired to date suggest that a spike in mechanotransductive ATP due to a suddenly applied increase in shear stress occurs in blood drawn from only 14% of the population.
Highlights
We show that Red blood cell (RBC) drawn from n = 15 different participants all exhibited shear- induced Adenosine triphosphate (ATP) release, consistent with previous results by numerous researchers who employed a variety of different mechanical stimuli
Wclc + ww(x − lc) where Q = 3 μL/min is the flow rate, h = 37 μm is the height of the microfluidic channel, wc = 20 μm is the width of the constriction region, lc = 800 μm is the length of the constriction region, ww = 100 μm is the width of the wide region, and x is the distance travelled from the constriction
Five of the peaks we observe in this work occur at x ≈ 2750 μm, the remainder occur near the end of our microfluidic channel (x > 6000 μm)
Summary
Despite the traditional view of RBCs as passive carriers of oxygen, recent work has demonstrated that RBCs are active sensors of local circulatory conditions so that they can perform an important role in regulating local blood flow in the microvasculature.[1,2,3] RBCs have been shown to release ATP in response to hypoxia,[1,4,5,6]. It is clear from the large body of results acquired in filter paper experiments,[2,20,21] microbore tubing experiments,[7,8,23] and various microfluidic geometries[9,10,11] that shear-induced ATP release by RBCs is a significant contributor to extracellular ATP Those experiments all involve increased shear stress of relatively long duration compared to the short constriction employed by Wan et al[12] and Cinar et al[13] used exactly the same short constriction geometry as Wan et al,[12] yet did not observe a large spike in ATP. Taking this work in conjunction with the previous efforts of Wan et al[12] and Cinar et al,[13] it appears that a pronounced spike in ATP mechanotransduction in response to a suddenly applied shear increase only occurs in RBCs drawn from about 14% of the population
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