Nanotopography Enhances Dynamic Remodeling of Tight Junction Proteins through Cytosolic Liquid Complexes.
Nanotopography Enhances Dynamic Remodeling of Tight Junction Proteins through Cytosolic Liquid Complexes.
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DOI：
10.1021/acsnano.0c04866
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发表时间：
2020-10-27
期刊：
影响因子：
17.1
通讯作者：
Desai TA
中科院分区：
文献类型：
--
作者：
Huang X;Shi X;Hansen ME;Setiady I;Nemeth CL;Celli A;Huang B;Mauro T;Koval M;Desai TA
纳米地形材料提供了特殊的生物物理刺激，可以调节上皮紧密连接及其屏障功能。通过使用活细胞的全内反射荧光显微镜，我们证明了在上皮单层的顶端表面与定义的纳米形貌的合成表面的接触增加了大分子的细胞旁渗透性。为了监测活细胞中紧密连接形态的变化，我们通过基于CRISPR/Cas9的基因编辑对支架蛋白紧密连接蛋白-1（ZO-1）进行荧光标记，以使活细胞能够跟踪在生理水平表达的ZO-1。细胞和纳米结构表面之间的接触使连接相关的ZO-1不稳定，并促进其排列成直径1-5 μm的高度动态液体胞质复合物。连接相关的ZO-1迅速重塑，我们观察到的直接转化为连接样结构的胞质复合物。紧密连接蛋白家族的紧密连接跨膜蛋白和F-肌动蛋白也与这些ZO-1含有胞质复合物。这些数据表明，这些胞质结构是重要的中间体形成的nanotopographic线索，促进快速紧密连接重塑，以调节细胞旁通透性。
Nanotopographic materials provide special biophysical stimuli that can regulate epithelial tight junctions and their barrier function. Through the use of total internal reflection fluorescence microscopy of live cells, we demonstrated that contact of synthetic surfaces with defined nanotopography at the apical surface of epithelial monolayers increased paracellular permeability of macromolecules. To monitor changes in tight junction morphology in live cells, we fluorescently tagged the scaffold protein zonula occludens-1 (ZO-1) through CRISPR/Cas9-based gene editing to enable live cell tracking of ZO-1 expressed at physiologic levels. Contact between cells and nanostructured surfaces destabilized junction-associated ZO-1 and promoted its arrangement into highly dynamic liquid cytosolic complexes with a 1–5 μm diameter. Junction-associated ZO-1 rapidly remodeled, and we observed the direct transformation of cytosolic complexes into junction-like structures. Claudin-family tight junction transmembrane proteins and F-actin also were associated with these ZO-1 containing cytosolic complexes. These data suggest that these cytosolic structures are important intermediates formed in response to nanotopographic cues that facilitate rapid tight junction remodeling in order to regulate paracellular permeability.
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影响因子：
11.8
作者：
Belardi B;Hamkins-Indik T;Harris AR;Kim J;Xu K;Fletcher DA
通讯作者：
Fletcher DA
影响因子：
14
作者：
Krug, Susanne M.;Amasheh, Maren;Amasheh, Salah
通讯作者：
Amasheh, Salah
DOI：
10.1152/ajplung.00299.2010
发表时间：
2011-07-01
影响因子：
4.9
作者：
Mitchell, Leslie A.;Overgaard, Christian E.;Koval, Michael
通讯作者：
Koval, Michael
影响因子：
10.8
作者：
Kam, Kimberly R.;Walsh, Laura A.;Desai, Tejal A.
通讯作者：
Desai, Tejal A.
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K