Cells function as a ternary logic gate to decide migration direction under integrated chemical and fluidic cues.

Cells function as a ternary logic gate to decide migration direction under integrated chemical and fluidic cues.
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DOI:
10.1039/d2lc00807f
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发表时间:
2023-02-14
期刊:
影响因子:
6.1
通讯作者:
--
中科院分区:
工程技术1区
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在许多生理和病理过程中,细胞感受到各种环境信号并随后处理细胞内信号以决定其迁移方向。虽然已经在这些定向迁移中鉴定了几种信号分子和网络,但是在多种和综合的线索(特别是化学和流体线索)下预测迁移方向仍然是模糊的。在这里,我们研究了细胞信号处理机制,通过逆向工程定向细胞迁移下集成的化学和流体线索。我们使用微流体平台将受控的化学和流体线索施加到细胞,并分析了细胞检测限方面的线索的细胞外偶联。然后,对细胞的迁移行为进行逆向工程,以建立一个细胞信号处理系统作为逻辑门,该系统基于“选择”门。这个框架进一步讨论了一个最小的细胞内信号网络的共享途径模型。提出的三进制逻辑门的框架提出了一个系统的观点,以了解细胞如何解码多个线索,并作出决定的迁移方向。定向细胞迁移的逆向工程系统生物学框架,其中细胞用作三元逻辑门来解码纠缠的化学和流体线索以确定迁移方向。
Cells sense various environmental cues and subsequently process intracellular signals to decide their migration direction in many physiological and pathological processes. Although several signaling molecules and networks have been identified in these directed migrations, it still remains ambiguous to predict the migration direction under multiple and integrated cues, specifically chemical and fluidic cues. Here, we investigated the cellular signal processing machinery by reverse-engineering directed cell migration under integrated chemical and fluidic cues. We imposed controlled chemical and fluidic cues to cells using a microfluidic platform and analyzed the extracellular coupling of the cues with respect to the cellular detection limit. Then, the cell's migratory behavior was reverse-engineered to build a cellular signal processing system as a logic gate, which is based on a “selection” gate. This framework is further discussed with a minimal intracellular signaling network of a shared pathway model. The proposed framework of the ternary logic gate suggests a systematic view to understand how cells decode multiple cues and make decisions about the migration direction. A reverse-engineered systems biology framework of directed cell migration in which cells function as a ternary logic gate to decode entangled chemical and fluidic cues to determine migration direction.
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