Nuclear lamina strain states revealed by intermolecular force biosensor.
Nuclear lamina strain states revealed by intermolecular force biosensor.
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DOI：
10.1038/s41467-023-39563-6
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发表时间：
2023-06-30
影响因子：
16.6
通讯作者：
Ihalainen, Teemu O. O.
中科院分区：
文献类型：
--
作者：
Danielsson, Brooke E. E.;Abraham, Bobin George;Mantyla, Elina;Cabe, Jolene I. I.;Mayer, Carl R. R.;Rekonen, Anna;Ek, Frans;Conway, Daniel E. E.;Ihalainen, Teemu O. O.
核膜一直被认为是核的重要结构元素。核层被认为既可以保护DNA免受过度机械力的影响，也可以将机械力传递到DNA上。然而，到目前为止，还没有一种技术方法来在蛋白质水平上直接测量核板层上的机械力。为了克服这一局限性，我们开发了一种基于纳米体的分子间张力FRET生物传感器，能够测量层粘连蛋白细丝的机械应变。使用这个传感器，我们能够显示核层受到很大的力。这些力依赖于核体积、肌球蛋白收缩能力、功能性LINC复合体、染色质缩合状态、细胞周期和EMT。有趣的是，核质层上也存在很大的力，这表明这些层可能在核中也有重要的机械作用。总体而言，我们证明了基于纳米体的方法可以构建用于机械生物学研究的复杂蛋白质结构的生物传感器。在这项工作中，基于纳米体的分子间应变传感器被用来跟踪核层中的机械应变。结果表明，核膜的力学状态不仅与细胞的收缩性能有关，还与染色质的堆积有关。
Nuclear lamins have been considered an important structural element of the nucleus. The nuclear lamina is thought both to shield DNA from excessive mechanical forces and to transmit mechanical forces onto the DNA. However, to date there is not yet a technical approach to directly measure mechanical forces on nuclear lamins at the protein level. To overcome this limitation, we developed a nanobody-based intermolecular tension FRET biosensor capable of measuring the mechanical strain of lamin filaments. Using this sensor, we were able to show that the nuclear lamina is subjected to significant force. These forces are dependent on nuclear volume, actomyosin contractility, functional LINC complex, chromatin condensation state, cell cycle, and EMT. Interestingly, large forces were also present on nucleoplasmic lamins, indicating that these lamins may also have an important mechanical role in the nucleus. Overall, we demonstrate that the nanobody-based approach allows construction of biosensors for complex protein structures for mechanobiology studies. In this work, a nanobody based intermolecular strain sensor was used to follow the mechanical strain in the nuclear lamina. The results indicate that mechanical state of the nuclear lamina is not only affected by the cell contractility, but also chromatin packing.
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DOI：
10.1083/jcb.201908036
发表时间：
2020-10-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Déjardin T;Carollo PS;Sipieter F;Davidson PM;Seiler C;Cuvelier D;Cadot B;Sykes C;Gomes ER;Borghi N
通讯作者：
Borghi N
影响因子：
41.2
作者：
Ihalainen TO;Aires L;Herzog FA;Schwartlander R;Moeller J;Vogel V
通讯作者：
Vogel V
影响因子：
21.3
作者：
Austen K;Ringer P;Mehlich A;Chrostek-Grashoff A;Kluger C;Klingner C;Sabass B;Zent R;Rief M;Grashoff C
通讯作者：
Grashoff C
影响因子：
6
作者：
Baddam SR;Arsenovic PT;Narayanan V;Duggan NR;Mayer CR;Newman ST;Abutaleb DA;Mohan A;Kowalczyk AP;Conway DE
通讯作者：
Conway DE
影响因子：
4.7
作者：
Cao, Penghui;Tao, Weiwei;Park, Harold S.
通讯作者：
Park, Harold S.