Multimodal imaging of fluid transport in living epithelial sheets

K. Webb, Jing Zhang, M. Somekh
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Abstract

Epithelial tissues form the barrier between different fluid compartments throughout the body, lining and delineating the borders between tissues to control homeostasis and provide for the functions of secretion, absorption, and volume regulation. Key to these physiological roles is the transepithelial transport of fluid and solutes. Vectorial transport is possible due to the highly polarised cytoarchitecture, with different ion transporters and other proteins present in the apical vs basolateral membrane domains, which are separated by “tight junctions” which ring the lateral membranes of each cell. These separate the apical and basolateral compartments, providing intercellular adhesion and controlling permeation via the intercellular pathway. By varying the composition and function of the pools of transport proteins between these segregated membrane domains, directed transport is achieved thus promoting homeostasis. The retinal pigment epithelium (RPE) lies behind the neural retina, forming the blood-retinal barrier and providing for the homeostasitic and biochemical support of the photoreceptors and other neuronal layers. Much is known of RPE physiology at the macroscopic level since dysregulation or pathology have profound consequences for the visual system. Lacking is the detailed knowledge of biophysical mechanisms and local intercompartmental dynamics by which fluid and solute transport is achieved and regulated at the cellular and subcellular level.
活体上皮细胞内液体运输的多模态成像
上皮组织在全身不同的液体室之间形成屏障,在组织之间形成边界,控制体内平衡,并提供分泌、吸收和体积调节功能。这些生理作用的关键是液体和溶质的经上皮运输。载体运输是可能的,因为高度极化的细胞结构,不同的离子转运体和其他蛋白质存在于顶端和基底外侧膜域,它们被“紧密连接”分开,这些“紧密连接”环绕着每个细胞的外侧膜。它们将细胞顶室和基底外侧室分开,提供细胞间粘附并通过细胞间通路控制渗透。通过改变这些分离膜结构域之间转运蛋白池的组成和功能,实现了定向转运,从而促进了体内平衡。视网膜色素上皮(RPE)位于神经视网膜后面,形成血视网膜屏障,为光感受器和其他神经元层提供稳态和生化支持。由于失调或病理对视觉系统有深远的影响,因此在宏观水平上对RPE生理学有很多了解。缺乏生物物理机制和局部室间动力学的详细知识,通过这些机制,流体和溶质运输在细胞和亚细胞水平上实现和调节。
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