Do Skeletal Dynamics Mediate Sugar Uptake and Transport in Human Erythrocytes?
Do Skeletal Dynamics Mediate Sugar Uptake and Transport in Human Erythrocytes?
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骨骼动力学是否介导人类红细胞的糖摄取和运输？
DOI：
10.1016/j.bpj.2018.01.041
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发表时间：
2018
影响因子：
3.4
通讯作者：
Carruthers,Anthony
中科院分区：
文献类型：
--
作者：
Asaro,RobertJ;Zhu,Qiang;Cabrales,Pedro;Carruthers,Anthony
在此，我们探讨了这样的假设：分子或离子转运到红细胞中可能受到血影蛋白/肌动蛋白骨架的动力学影响和直接刺激。骨骼/肌动蛋白运动由热波动驱动，热波动可能受到 ATP 水解以及连接骨骼和细胞脂膜的连接复合物结构变化的影响。具体来说，我们重点关注通过葡萄糖转运蛋白 1 将葡萄糖摄取到红细胞中，以及葡萄糖转运蛋白 1 内面侧葡萄糖解离的动力学。我们认为，葡萄糖解离受到肌动蛋白/血影蛋白骨架诱导的水动力以及摆动的 37 nm 长 F-肌动蛋白原丝与葡萄糖可能接触的影响，我们将这种效应称为“粘球效应”。我们的假设和结果在 Carruthers 及其同事的动力学测量和隔室动力学模型的框架内进行了解释；这些实验结果和模型将葡萄糖解离描述为摄取过程中的“缓慢步骤”（即限速步骤）。我们的假设得到了进一步支持，即使用我们基于肌动蛋白/血影蛋白骨架的分子模型对骨架增强运输进行直接模拟，以及对受到剪切变形的细胞摄取葡萄糖的实验测量，这证明了平流的流体动力学效应。事实上，我们的模拟之前已经证明了细胞在剪切变形中的骨骼动力学增强，因为它们在骨骼内自然发生，这种效应也得到了实验观察的支持。
We explore, herein, the hypothesis that transport of molecules or ions into erythrocytes may be affected and directly stimulated by the dynamics of the spectrin/actin skeleton. Skeleton/actin motions are driven by thermal fluctuations that may be influenced by ATP hydrolysis as well as by structural alterations of the junctional complexes that connect the skeleton to the cell's lipid membrane. Specifically, we focus on the uptake of glucose into erythrocytes via glucose transporter 1 and on the kinetics of glucose disassociation at the endofacial side of glucose transporter 1. We argue that glucose disassociation is affected by both hydrodynamic forces induced by the actin/spectrin skeleton and by probable contact of the swinging 37-nm-long F-actin protofilament with glucose, an effect we dub the "stickball effect." Our hypothesis and results are interpreted within the framework of the kinetic measurements and compartmental kinetic models of Carruthers and co-workers; these experimental results and models describe glucose disassociation as the "slow step" (i.e., rate-limiting step) in the uptake process. Our hypothesis is further supported by direct simulations of skeleton-enhanced transport using our molecular-based models for the actin/spectrin skeleton as well as by experimental measurements of glucose uptake into cells subject to shear deformations, which demonstrate the hydrodynamic effects of advection. Our simulations have, in fact, previously demonstrated enhanced skeletal dynamics in cells in shear deformations, as they occur naturally within the skeleton, which is an effect also supported by experimental observations.