Intracellular Concentration Gradients That Mirror External Gradients in Microfluidic Flows: A Computational Analysis
Intracellular Concentration Gradients That Mirror External Gradients in Microfluidic Flows: A Computational Analysis
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DOI：
10.1007/s12195-016-0474-3
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发表时间：
2017-04-01
影响因子：
2.8
通讯作者：
Lele, Tanmay P.
中科院分区：
文献类型：
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作者：
Aggarwal, Varun;Lele, Tanmay P.
产生稳定的细胞内浓度梯度是局部控制细胞功能、选择性操纵细胞结构和测试与细胞内动态过程有关的假设的有用方法。微流控装置中的细胞培养允许在单个细胞中呈现稳定的小分子梯度。这种方法已经被用来选择性地标记细胞部分的线粒体，胰蛋白酶化特定的细胞结构域，并在细胞的特定部分触发受体介导的内吞作用。考虑到典型细胞的小长度尺度（类似于30 μ m）和小分子的短细胞质扩散时间尺度，这种方法可以局部标记细胞是令人惊讶的。在这里，我们开发了模型来探索在微流体装置中可以维持稳定的细胞内浓度梯度的参数空间。我们表明，与扩散相比，当膜上的传质速率较高时，即舍伍德数大于1时，梯度可以无限发展并保持。我们展示了这些梯度如何导致配体-受体结合和酶底物结合的梯度。这一分析有助于解释和设计细胞质分配的微流控实验。
The generation of stable intracellular concentration gradients is a useful method for local control of cell function, selective manipulation of cellular structures and testing hypotheses related to dynamical intracellular processes. Cell culture in a microfluidic device allows the presentation of a stable gradient of small molecules across a single cell. This method has been used to selectively label mitochondria in portions of the cell, trypsinize specific cellular domains, and trigger receptor-mediated endocytosis in specific portions of the cell. Given the small length scales of a typical cell (similar to 30 mu m) and short cytoplasmic diffusive time scales of small molecules, it is surprising that cells can be labeled locally with this method. Here we developed models to explore the parametric space over which stable intracellular concentration gradients can be maintained in a microfluidic device. We show that gradients can develop and be maintained indefinitely for high rates of mass transfer across the membrane compared with diffusion, that is, for Sherwood number greater than 1. We show how these gradients can result in gradients in ligand-receptor binding and enzyme substrate binding. This analysis can help interpret and design microfluidic experiments for cytoplasmic partitioning.