Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Nat Microbiol. 2019 Aug;4(8):1274-1281. doi: 10.1038/s41564-019-0455-0. Epub 2019 May 13.
Multiple cell types sense fluid flow as an environmental cue. Flow can exert shear force (or stress) on cells, and the prevailing model is that biological flow sensing involves the measurement of shear force. Here, we provide evidence for force-independent flow sensing in the bacterium Pseudomonas aeruginosa. A microfluidic-based transcriptomic approach enabled us to discover an operon of P. aeruginosa that is rapidly and robustly upregulated in response to flow. Using a single-cell reporter of this operon, which we name the flow-regulated operon (fro), we establish that P. aeruginosa dynamically tunes gene expression to flow intensity through a process we call rheosensing (as rheo- is Greek for flow). We further show that rheosensing occurs in multicellular biofilms, involves signalling through the alternative sigma factor FroR, and does not require known surface sensors. To directly test whether rheosensing measures force, we independently altered the two parameters that contribute to shear stress: shear rate and solution viscosity. Surprisingly, we discovered that rheosensing is sensitive to shear rate but not viscosity, indicating that rheosensing is a kinematic (force-independent) form of mechanosensing. Thus, our findings challenge the dominant belief that biological mechanosensing requires the measurement of forces.
多种细胞类型将流体流动视为环境线索。流动可以对细胞施加剪切力（或应力），而流行的模型是生物流动感应涉及剪切力的测量。在这里，我们为假单胞菌中的力独立流动感应提供了证据。一种基于微流控的转录组学方法使我们能够发现假单胞菌中的一个操纵子，该操纵子对流动的快速和强烈反应而上调。使用该操纵子的单细胞报告器，我们将其命名为流动调节操纵子（fro），我们确定假单胞菌通过我们称之为流感（因为 rheo 是希腊语中的流动）的过程动态地将基因表达调整为流动强度。我们进一步表明，流感发生在多细胞生物膜中，涉及通过替代 sigma 因子 FroR 进行信号传递，并且不需要已知的表面传感器。为了直接测试流感是否测量力，我们独立改变了导致剪切应力的两个参数：剪切率和溶液粘度。令人惊讶的是，我们发现流感对剪切率敏感，但对粘度不敏感，这表明流感是一种运动学（力独立）形式的机械感应。因此，我们的发现挑战了生物机械感应需要测量力的主导信念。
