Mechanical diagnosis of human erythrocytes by ultra-high speed manipulation unraveled critical time window for global cytoskeletal remodeling.
Mechanical diagnosis of human erythrocytes by ultra-high speed manipulation unraveled critical time window for global cytoskeletal remodeling.
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DOI：
10.1038/srep43134
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发表时间：
2017-02-24
影响因子：
4.6
通讯作者：
Tanaka M
中科院分区：
文献类型：
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作者：
Ito H;Murakami R;Sakuma S;Tsai CD;Gutsmann T;Brandenburg K;Pöschl JM;Arai F;Kaneko M;Tanaka M
红细胞在微血管中的大变形性是实现畅通循环的前提。我们开发了一种基于微流控“机器人泵”的超高速位置控制的新型工具，用于对人类红细胞进行三步“捕捉-加载-发射”操作。定量的红细胞形状恢复作为加载时间的函数揭示了快速恢复和缓慢恢复之间转换的关键时间窗口。与耗竭三磷酸腺苷的红细胞的比较表明，整个细胞的细胞骨架重构发生的时间比单个血影蛋白结节的局部解离-再解离时间长3个数量级。最后，我们通过将红细胞与内毒素孵育来模拟脓毒症条件，发现暴露在内毒素下会导致细胞骨架重塑的特征过渡时间显著延迟。利用机器人泵技术对红细胞进行高速操作，可以实现血液相关疾病的高通量机械诊断。
Large deformability of erythrocytes in microvasculature is a prerequisite to realize smooth circulation. We develop a novel tool for the three-step “Catch-Load-Launch” manipulation of a human erythrocyte based on an ultra-high speed position control by a microfluidic “robotic pump”. Quantification of the erythrocyte shape recovery as a function of loading time uncovered the critical time window for the transition between fast and slow recoveries. The comparison with erythrocytes under depletion of adenosine triphosphate revealed that the cytoskeletal remodeling over a whole cell occurs in 3 orders of magnitude longer timescale than the local dissociation-reassociation of a single spectrin node. Finally, we modeled septic conditions by incubating erythrocytes with endotoxin, and found that the exposure to endotoxin results in a significant delay in the characteristic transition time for cytoskeletal remodeling. The high speed manipulation of erythrocytes with a robotic pump technique allows for high throughput mechanical diagnosis of blood-related diseases.