Podocyte injury elicits loss and recovery of cellular forces.
Podocyte injury elicits loss and recovery of cellular forces.
复制标题
DOI：
10.1126/sciadv.aap8030
复制
发表时间：
2018-06
期刊：
影响因子：
13.6
通讯作者：
Reynolds PA
中科院分区：
文献类型：
--
作者：
Haley KE;Kronenberg NM;Liehm P;Elshani M;Bell C;Harrison DJ;Gather MC;Reynolds PA
ERISIS在急性肾损伤模型中连续绘制足细胞施加在其底物上的力的动态变化。在健康的肾脏中，被称为足细胞的特殊细胞形成了一个复杂的血液过滤装置，允许从血液中排泄废物和多余的液体，同时防止白蛋白等蛋白质的损失。为了有效地运行，该过滤器处于相当大的静液压机械压力下。考虑到足细胞的功能，施加机械力的能力对足细胞的生存至关重要。然而，到目前为止，足细胞机械生物学仍然知之甚少，这主要是因为缺乏关于相关力量的实验数据。我们使用最近推出的用于连续测力的功能成像设备，实时地对分化的足细胞施加的力进行定量、连续、无干扰和高分辨率的测量。使用公认的足细胞损伤模型，我们发现损伤的足细胞经历了几乎完全的细胞力传递的丧失，但这种力的丧失在某些条件下是可逆的。观察到的力量变化与F-肌动蛋白重排和足细胞特异性蛋白表达减少有关。通过引入稳健和高通量的机械表型，并通过论证机械力在足细胞损伤中的重要性，这项研究为进一步了解肾脏铺平了道路。此外，在已建立的力映射技术的基础上，我们将细胞力测量与免疫荧光相结合，并对细胞群体进行连续的长期力测量。因此，我们的方法对涉及机械力的广泛的生物医学问题具有普遍的适用性。
ERISM continuously maps dynamic changes in the forces podocytes exert on their substrate in a model of acute kidney damage. In the healthy kidney, specialized cells called podocytes form a sophisticated blood filtration apparatus that allows excretion of wastes and excess fluid from the blood while preventing loss of proteins such as albumin. To operate effectively, this filter is under substantial hydrostatic mechanical pressure. Given their function, it is expected that the ability to apply mechanical force is crucial to the survival of podocytes. However, to date, podocyte mechanobiology remains poorly understood, largely because of a lack of experimental data on the forces involved. We perform quantitative, continuous, nondisruptive, and high-resolution measurements of the forces exerted by differentiated podocytes in real time using a recently introduced functional imaging modality for continuous force mapping. Using an accepted model for podocyte injury, we find that injured podocytes experience near-complete loss of cellular force transmission but that this loss of force is reversible under certain conditions. The observed changes in force correlate with F-actin rearrangement and reduced expression of podocyte-specific proteins. By introducing robust and high-throughput mechanical phenotyping and by demonstrating the significance of mechanical forces in podocyte injury, this research paves the way to a new level of understanding of the kidney. In addition, in an advance over established force mapping techniques, we integrate cellular force measurements with immunofluorescence and perform continuous long-term force measurements of a cell population. Hence, our approach has general applicability to a wide range of biomedical questions involving mechanical forces.
登录
查看更多内容
影响因子：
19.6
作者：
MEYER, TW;ANDERSON, S;BRENNER, BM
通讯作者：
BRENNER, BM
影响因子：
3.7
作者：
Embry AE;Mohammadi H;Niu X;Liu L;Moe B;Miller-Little WA;Lu CY;Bruggeman LA;McCulloch CA;Janmey PA;Miller RT
通讯作者：
Miller RT
影响因子：
1.2
作者：
Miyauchi, Masaaki;Toyoda, Masao;Suzuki, Daisuke
通讯作者：
Suzuki, Daisuke
影响因子：
19.6
作者：
ELLIS, EN;STEFFES, MW;MAUER, SM
通讯作者：
MAUER, SM
影响因子：
19.6
作者：
Petermann, AT;Krofft, R;Shankland, SJ
通讯作者：
Shankland, SJ