Chemotropism is an essential response of organisms to external chemical gradients that direct the growth of cells toward the gradient source. Chemotropic responses between single cells have been studied using in vitro gradients of synthetically derived signaling molecules and helped to develop a better understanding of chemotropism in multiple organisms. However, dynamic changes including spatial changes to the gradient as well as fluctuations in levels of cell generated signaling molecules can result in the redirection of chemotropic responses, which can be difficult to model with synthetic peptides and single cells. An experimental system that brings together populations of cells to monitor the population-scale chemotropic responses yet retain single cell spatiotemporal resolution would be useful to further inform on models of chemotropism. Here, we describe a microfluidic platform that can measure the chemotropic response between populations of mating yeast A- and α-cells with spatiotemporal programmability and sensitivity by positioning cell populations side by side in calcium alginate hydrogels along semipermeable membranes with micrometer spatial control. The mating phenotypes of the yeast populations were clearly observed over hours. Three distinct responses were observed depending on the distance between the A- and α-cell populations: the cells either continued to divide, arrest, and develop a stereotypical polarized projection termed a "shmoo" toward the cells of opposite mating type or formed shmoos in random directions. The results from our studies of yeast mating suggest that the biofabricated microfluidic platform can be adopted to study population-scale, spatial-sensitive cell-cell signaling behaviors that would be challenging using conventional approaches.

中文翻译：

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在生物装配的微流控平台中具有时空分辨率的酵母细胞群体之间的趋化性。

趋化性是生物体对外部化学梯度的基本反应，外部化学梯度将细胞的生长引向梯度源。已使用合成衍生的信号分子的体外梯度研究了单细胞之间的趋化性反应，有助于更好地了解多种生物的趋化性。但是，动态变化（包括梯度的空间变化以及细胞生成的信号分子水平的波动）可能导致趋化反应的重定向，这可能很难用合成肽和单细胞建模。一个将细胞群体聚集在一起以监测群体规模的趋化反应但保留单细胞时空分辨率的实验系统，对于进一步指导趋化模型很有用。这里，我们描述了一种微流控平台，该平台可以通过沿藻类钙盐水凝胶沿半透膜并排放置并通过千分尺空间控制，来测量交配的酵母A细胞和α细胞的群体之间的化学反应，并具有时空可编程性和敏感性。在数小时内清楚地观察到了酵母群体的交配表型。根据A细胞和α细胞群体之间的距离，观察到三个不同的反应：细胞继续分裂，停滞并向定型的极化投影朝着相反交配型的细胞或形成的shmoos形成“ shmoo”。随机方向。我们对酵母菌交配的研究结果表明，可采用生物制造的微流体平台来研究种群规模，