Viscoelastic behavior of human lamin A proteins in the context of dilated cardiomyopathy.

Viscoelastic behavior of human lamin A proteins in the context of dilated cardiomyopathy.
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DOI:
10.1371/journal.pone.0083410
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sengupta K
Sengupta K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Banerjee A;Rathee V;Krishnaswamy R;Bhattacharjee P;Ray P;Sood AK;Sengupta K

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核纤层蛋白是V型的中间丝蛋白,其构成核纤层或丝状网,其内衬于内核膜的核质侧。这种蛋白质网为核膜提供了一个支撑支架,并将间期染色体拴在核周围。发现主要是A型核纤层蛋白的突变是至少11种统称为核纤层蛋白病的人类疾病的病因,其中大多数核纤层蛋白病的特征在于具有改变的结构刚性、变形性和差的机械转导行为的异常核。但是,对层粘连蛋白A的粘弹性行为的研究仍然回避该领域。为了解决这个问题,我们在此提出了第一份报告的粘弹性野生型人类核纤层蛋白A和它的一些突变体与扩张型心肌病(DCM)使用定量流变学测量。我们观察到一个戏剧性的应变软化效应层A网络的应变振幅扫描测量的结果,这可能会出现从网络中的准交联或层A棒的大顺应性。此外,旋转和振荡剪切应力叠加时的微分弹性模量的急剧硬化反映了横向相关的层A杆的刚度的增加。这些研究结果提出了一个初步的见解不同的生物力学特性的野生型核纤层蛋白A蛋白及其突变体,这反过来又揭示了有趣的差异。
Lamins are intermediate filament proteins of type V constituting a nuclear lamina or filamentous meshwork which lines the nucleoplasmic side of the inner nuclear membrane. This protein mesh provides a supporting scaffold for the nuclear envelope and tethers interphase chromosome to the nuclear periphery. Mutations of mainly A-type lamins are found to be causative for at least 11 human diseases collectively termed as laminopathies majority of which are characterised by aberrant nuclei with altered structural rigidity, deformability and poor mechanotransduction behaviour. But the investigation of viscoelastic behavior of lamin A continues to elude the field. In order to address this problem, we hereby present the very first report on viscoelastic properties of wild type human lamin A and some of its mutants linked with Dilated cardiomyopathy (DCM) using quantitative rheological measurements. We observed a dramatic strain-softening effect on lamin A network as an outcome of the strain amplitude sweep measurements which could arise from the large compliance of the quasi-cross-links in the network or that of the lamin A rods. In addition, the drastic stiffening of the differential elastic moduli on superposition of rotational and oscillatory shear stress reflect the increase in the stiffness of the laterally associated lamin A rods. These findings present a preliminary insight into distinct biomechanical properties of wild type lamin A protein and its mutants which in turn revealed interesting differences.
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期刊: BIOCHEMISTRY
影响因子: 2.9
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