Cellular regulation of viscosity

粘度是生物化学反应的基础，因此，生命本身。温度影响 分子的扩散速率，并反过来调节非生命系统中的反应速率。几十年来， 假设生物体中的细胞受到与温度相同的原理的影响， 粘度、扩散和反应速率。然而，令人难以置信的复杂的基于扩散的 细胞的相互作用网络对这些波动是鲁棒的，因为即使在一个细胞中， 该通路具有影响细胞功能的多个方面的潜力。调节细胞内 粘度作为一种策略，以减轻扩散的变化，由于环境已在很大程度上 未开发的该提案解决了细胞内粘度如何被主动调节、 细胞过程中的粘度和疾病中的粘度失调。 我们最近发现，细胞溶质扩散速率和粘度控制的反应速率举行 在酿酒酵母中，在至少20° C的稳态温度下不变。我们发现 细胞粘度响应急性应激而暂时增加。我们将这种现象命名为 “粘性适应”。粘度适应是一种维持恒定粘度的稳态机制， 尽管温度波动以及对各种环境应激源的急性反应。 粘性适应通过产生粘性碳水化合物糖原起作用，该糖原与人类健康有关， 疾病，我们假设低能量水平触发粘适应。 粘适应的发现标志着我们对细胞如何调节的理解取得了重大进展 它们的生物物理特性。然而，许多谜团仍然存在，包括1）粘适应如何影响生物物理 细胞的特性，2）什么信号通路调节粘适应。我们建议（目标1）研究 糖原对蛋白质运动和结构的影响（目的2）研究如何调节途径 酵母和人体细胞中的粘度。 拟议的研究将审查一个基本的，但在很大程度上未探索的生物物理调节 细胞的特性，粘度。这将阐明长期被忽视的贡献粘度的关键细胞 这一基本特性在细胞中被积极调节的过程和机制。在这样做时， 这项工作有可能从粘度失调的角度重新构建疾病状况， 开创了“粘度相关”病理学的新概念框架。

Viscosity is fundamental to biochemical reactions and hence, life itself. Temperature affects the diffusion rate of molecules and in turn modulates the rate of reactions in non-living systems. For decades it has been assumed that cells in living organisms are subject to the same principles that connect temperature, viscosity, diffusion and reaction rates. Yet it has been a mystery how the incredibly complex diffusion-based interaction networks of a cell are robust to these fluctuations, since perturbation of reaction kinetics in even one pathway has the potential to impact multiple aspects of cellular functioning. The regulation of intracellular viscosity as a strategy to mitigate changes in diffusion due to the environment has been largely unexplored. This proposal addresses how intracellular viscosity is actively regulated, the effects of viscosity on cellular processes, and viscosity dysregulation in disease. We recently discovered that cytosolic diffusion rates and viscosity-controlled reaction rates are held invariant across at least 20° C of steady state temperatures in Saccharomyces cerevisiae. We found that cellular viscosity temporarily increases in response to acute stress. We named this phenomenon “viscoadaptation”. Viscoadaptation is both a homeostatic mechanism for maintaining constant viscosity despite fluctuations in temperature as well as an acute response to a variety of environmental stressors. Viscoadaptation acts via production of the viscous carbohydrate glycogen that is linked to human health and disease, and we hypothesize that low energy levels trigger viscoadaptation. The discovery of viscoadaptation marks a major advance in our understanding of how cells regulate their biophysical properties. Yet many mysteries remain, including 1) how viscodaptation affects the biophysical properties of cells, 2) what signaling pathways regulate viscoadaptation. We propose to (aim 1) study the effect of glycogen on protein mobility and structure (aim 2) investigate how the pathways regulating viscosity in yeast and human cells. The proposed studies will examine regulation of a fundamental yet largely unexplored biophysical feature of cells, viscosity. This will elucidate the long overlooked contribution of viscosity to critical cellular processes and the mechanisms by which this fundamental property is actively regulated in cells. In doing so, this work has the potential to reframe disease conditions from the perspective of viscosity dysregulation and usher in a new conceptual framework of "viscosity-related" pathologies.