title: Viscoelastic behavior of human lamin A proteins in the context of dilated cardiomyopathy.
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.
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, West Bengal, India.
authors.forename: Avinanda
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Physics, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Rathee
authors.affiliation: Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur Campus, Bangalore, Karnataka, India.
authors.forename: Rema
authors.initials: R
authors.lastname: Krishnaswamy
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, West Bengal, India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, West Bengal, India.
authors.forename: Pulak
authors.initials: P
authors.lastname: Ray
authors.affiliation: Department of Physics, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, West Bengal, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Sengupta
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D004548:Elasticity; D015870:Gene Expression; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D017510:Protein Folding; D033081:Shear Strength; D014783:Viscosity
chemical_list: D034904:Lamin Type A