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

PLoS One. 2013 Dec 30;8(12):e83410. doi: 10.1371/journal.pone.0083410. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / pathology*
  • Cell Line
  • Elasticity
  • Gene Expression
  • Humans
  • Lamin Type A / chemistry*
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Lamin Type A / ultrastructure
  • Mutation
  • Protein Folding
  • Shear Strength
  • Viscosity

Substances

  • Lamin Type A

Grant support

AB thanks University Grants Council, Government of India for the fellowship. AKS thanks Council of Scientific and Industrial Research, (Government of India) Bhatnagar Fellowship for support. RK thanks support under Ramanujan Fellowship, Department of Science and Technology, Government of India. KSG thanks MMDDA and BARD projects of Department of Atomic Energy, Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.