Stiffening of sickle cell trait red blood cells under simulated strenuous exercise conditions

Xu, Zhenghua; Zheng, Yi; Wang, Xian; Shehata, Nadine; Wang, Chen; Xie, Shaorong; Sun, Yu

doi:10.1038/micronano.2016.61

Cited by 10 publications

(9 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell deformability is gaining recognition as a novel cell state marker. Reduced cell deformability is commonly associated with a pathological phenotype, e.g., in malaria (Hosseini andFeng, 2012 andToepfner et al, 2018), sickle-cell disease (Xu et al, 2016), and thalassemia (Athanasiou et al, 1991). Additionally, deformability is seen as a valuable label-free marker associated with various cell activities, such as cell cycle regulation (Tsai et al, 1996), differentiation (Lin et al, 2017), metastasis (Ochalek et al, 1988), and leukocyte activation (Khismatullin, 2009).…”

Section: Discussionmentioning

confidence: 99%

Impact of poloxamer 188 (Pluronic F-68) additive on cell mechanical properties, quantification by real-time deformability cytometry

et al. 2018

View full text Add to dashboard Cite

Advances in cellular therapies have led to the development of new approaches for cell product purification and formulation, e.g., utilizing cell endogenous properties such as size and deformability as a basis for separation from potentially harmful undesirable by-products. However, commonly used additives such as Pluronic F-68 and other poloxamer macromolecules can change the mechanical properties of cells and consequently alter their processing. In this paper, we quantified the short-term effect of Pluronic F-68 on the mechanotype of three different cell types (Jurkat cells, red blood cells, and human embryonic kidney cells) using real-time deformability cytometry. The impact of the additive concentration was assessed in terms of cell size and deformability. We observed that cells respond progressively to the presence of Pluronic F-68 within first 3 h of incubation and become significantly stiffer (p-value < 0.001) in comparison to a serum-free control and a control containing serum. We also observed that the short-term response manifested as cell stiffening is true (p-value < 0.001) for the concentration reaching 1% (w/v) of the poloxamer additive in tested buffers. Additionally, using flow cytometry, we assessed that changes in cell deformability triggered by addition of Pluronic F-68 are not accompanied by size or viability alterations.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of poloxamer 188 (Pluronic F-68) additive on cell mechanical properties, quantification by real-time deformability cytometry

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The microfluidic device was fabricated via soft lithography and PDMS (Polydimethylsiloxane) molding according to our previously reported method 30 . Briefly, the device had a microchannel of 60 µm in height and 1000 µm in width.…”

Section: Methodsmentioning

confidence: 99%

“…Three to seven independent experimental replications were conducted for each tested condition. The shape of each individual RBC was measured via image processing in Matlab, and the shear modulus of each RBC was quantified, according to our previously reported method 30 . Briefly, according to the Kelvin–Voigt (KV) model, , where T (µN/m) is the average tension force acting on the RBC membrane, which was calculated from the shear stress applied on the RBC and the area of the RBC 34,35 ; λ is the extension ratio of the RBC membrane, , where l is the RBC’s length when deformed under shear stress; and l 0 is the RBC’s original length.…”

Section: Methodsmentioning

confidence: 99%

Stiffness and ATP recovery of stored red blood cells in serum

Dou

Wang

et al. 2019

Microsyst Nanoeng

Self Cite

View full text Add to dashboard Cite

In transfusion medicine, there has been a decades-long debate about whether the age of stored red blood cells (RBCs) is a factor in transfusion efficacy. Existing clinical studies investigating whether older RBCs cause worse clinical outcomes have provided conflicting information: some have shown that older blood is less effective, while others have shown no such difference. The controversial results could have been biased by the vastly different conditions of the patients involved in the clinical studies; however, another source of inconsistency is a lack of understanding of how well and quickly stored RBCs can recover their key parameters, such as stiffness and ATP concentration, after transfusion. In this work, we quantitatively studied the stiffness and ATP recovery of stored RBCs in 37 °C human serum. The results showed that in 37 °C human serum, stored RBCs are able to recover their stiffness and ATP concentration to varying extents depending on how long they have been stored. Fresher RBCs (1–3 weeks old) were found to have a significantly higher capacity for stiffness and ATP recovery in human serum than older RBCs (4–6 weeks old). For instance, for 1-week-old RBCs, although the shear modulus before recovery was 1.6 times that of fresh RBCs, 97% of the cells recovered in human serum to have 1.1 times the shear modulus of fresh RBCs, and the ATP concentration of 1-week-old RBCs after recovery showed no difference from that of fresh RBCs. However, for 6-week-old RBCs, only ~70% of the RBCs showed stiffness recovery in human serum; their shear modulus after recovery was still 2.1 times that of fresh RBCs; and their ATP concentration after recovery was 25% lower than that of fresh RBCs. Our experiments also revealed that the processes of stiffness recovery and ATP recovery took place on the scale of tens of minutes. We hope that this study will trigger the next steps of comprehensively characterizing the recovery behaviors of stored RBCs (e.g., recovery of normal 2,3-DPG [2,3-Diphosphoglycerate]and SNO [S-nitrosation] levels) and quantifying the in vivo recovery of stored RBCs in transfusion medicine.

show abstract

“…Before being introduced into the device, fresh RBCs and RBCs stored from 1 week to 6 weeks were diluted 200 times in phosphate-buffered saline (PBS) to minimize the coincidence occurrences of multiple cells in the channel. Although the pH of RBC storage medium decreases to 6.5 by the sixth week 19 , stored RBCs were tested in PBS (pH: 7.35) since pH 7.35 is more physiologically relevant 20 . Before RBCs were introduced into the microfluidic device, their shape at rest was first evaluated, as shown in Figure 1b The size of the constriction channel was chosen via finite element simulation and experimental validation.…”

Section: Methodsmentioning

confidence: 99%

Stiffness increase of red blood cells during storage

Zheng

Wang

et al. 2018

Microsyst Nanoeng

Self Cite

View full text Add to dashboard Cite

In transfusion medicine, the deformability of stored red blood cells (RBCs) changes during storage in blood banks. Compromised RBC deformability can reduce the transfusion efficiency or intensify transfusion complications, such as sepsis. This paper reports the microfluidic mechanical measurement of stored RBCs under the physiological deformation mode (that is, folding). Instead of using phenomenological metrics of deformation or elongation indices (DI or EI), the effective stiffness of RBCs, a flow velocityindependent parameter, is defined and used for the first time to evaluate the mechanical degradation of RBCs during storage. Fresh RBCs and RBCs stored up to 6 weeks (42 days) in the blood bank were measured, revealing that the effective stiffness of RBCs increases over the storage process. RBCs stored for 1 week started to show significantly higher stiffness than fresh RBCs, and stored RBC stiffness degraded faster during the last 3 weeks than during the first 3 weeks. Furthermore, the results indicate that the time points of the effective stiffness increase coincide well with the degradation patterns of S-nitrosothiols (SNO) and adenosine triphosphate (ATP) in RBC storage lesions.

show abstract

Stiffening of sickle cell trait red blood cells under simulated strenuous exercise conditions

Cited by 10 publications

References 43 publications

Impact of poloxamer 188 (Pluronic F-68) additive on cell mechanical properties, quantification by real-time deformability cytometry

Impact of poloxamer 188 (Pluronic F-68) additive on cell mechanical properties, quantification by real-time deformability cytometry

Stiffness and ATP recovery of stored red blood cells in serum

Stiffness increase of red blood cells during storage

Contact Info

Product

Resources

About