Active microrheology using pulsed optical tweezers to probe viscoelasticity of Lamin A

Soft Matter ◽  
2021 ◽  
Author(s):  
Chandrayee Mukherjee ◽  
Avijit Kundu ◽  
Raunak Dey ◽  
Ayan Banerjee ◽  
Kaushik Sengupta
Keyword(s):  
Optical Tweezers ◽  
Intermediate Filament ◽  
Mammalian Cells ◽  
Lamin A ◽  
Intermediate Filament Proteins ◽  
Type V

Lamins are nucleoskeletal proteins of mammalian cells that stabilize the structure and maintain the rigidity of the nucleus. These type V intermediate filament proteins which are predominantly of A and...

Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells

1995 ◽  
Vol 108 (2) ◽  
pp. 635-644 ◽  
Author(s):  
P. Hozak ◽  
A.M. Sasseville ◽  
Y. Raymond ◽  
P.R. Cook
Keyword(s):  
Nuclear Membrane ◽  
Intermediate Filament ◽  
Mammalian Cells ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Human Cells ◽  
Lamin A ◽  
Intermediate Filament Proteins ◽  
Form Part ◽  
Dense Chromatin

The nuclear lamina forms a protein mesh that underlies the nuclear membrane. In most mammalian cells it contains the intermediate filament proteins, lamins A, B and C. As their name indicates, lamins are generally thought to be confined to the nuclear periphery. We now show that they also form part of a diffuse skeleton that ramifies throughout the interior of the nucleus. Unlike their peripheral counterparts, these internal lamins are buried in dense chromatin and so are inaccessible to antibodies, but accessibility can be increased by removing chromatin. Knobs and nodes on an internal skeleton can then be immunolabelled using fluorescein- or gold-conjugated anti-lamin A antibodies. These results suggest that the lamins are misnamed as they are also found internally.

scholarly journals Active microrheology using pulsed optical tweezers to probe viscoelasticity of Lamin A towards diagnosis of laminopathies

2021 ◽  
Author(s):  
C. Mukherjee ◽  
A. Kundu ◽  
R. Dey ◽  
A. Banerjee ◽  
K. Sengupta
Keyword(s):  
Optical Tweezers ◽  
Intermediate Filament ◽  
The Body ◽  
Single Amino Acid ◽  
Elastic Behavior ◽  
Lamin A ◽  
Intermediate Filament Protein ◽  
Fast Method ◽  
Universal Method ◽  
Intermediate Filament Proteins

AbstractLamins are nucleoskeletal proteins of mammalian cells that stabilize the structure and maintain the rigidity of the nucleus. These type V intermediate filament proteins which are predominantly of A and B types provide necessary tensile strength to the nucleus. Single amino acid missense mutations occurring all over the lamin A protein form a cluster of human diseases termed as laminopathies, a few of which principally affect the muscle and cardiac tissues responsible for load bearing functionalities of the body. One such mutation is lamin A350P which causes dilated cardiomyopathy in patients. It is likely that a change from alanine to proline in the α-helical 2B rod domain of the protein might severely disrupt the propensity of the filaments to polymerise into functional higher order structures required to form a fully functional lamina with its characteristic elasticity. In this study, we validate for the very first time, the application of active microrheology employing oscillating optical tweezers to investigate any alterations in the visco-elastic parameters of the mutant protein meshwork in vitro, which might translate into possible changes in nuclear plasticity. We confirm our findings from this robust yet fast method by imaging both the wild type and mutant lamins using a super resolution microscope, and observe changes in the mesh size which explain our measured changes in the viscoelastic parameters of the lamins. This method could naturally be extended to conduct microrheological measurements on any intermediate filament protein or any protein endowed with elastic behavior, with minor schematic modifications, thus bearing significant implications in laminopathies and other diseases which are associated with changes in structural rigidity of any cellular organelle.SignificanceLamin A mutations produce an array of diseases termed as laminopathies which are primarily characterized by alteration of elastic behavior of the nucleus which in turn leads to defects in mechanotransduction. This is the first report in the lamin arena which shows a fast, accurate and direct quantification of elastic moduli of lamin A using optical tweezers-based microrheology. This has very significant implications and can be registered to be a robust and universal method that could also be suitably used for probing changes in elastic properties of any proteins or surfactants in a disease scenario such as SARS-Cov2 (Covid-19), which is pandemic at this time.

Expression patterns of intermediate filament proteins desmin and lamin A in the developing conduction system of early human embryonic hearts

2019 ◽  
Vol 236 (3) ◽  
pp. 540-548
Author(s):  
Hui‐Xia Liu ◽  
Yi‐Xin Jing ◽  
Jing‐Jing Wang ◽  
Yan‐Ping Yang ◽  
Yun‐Xiu Wang ◽  
...  
Keyword(s):  
Intermediate Filament ◽  
Expression Patterns ◽  
Conduction System ◽  
Lamin A ◽  
Intermediate Filament Proteins ◽  
Early Human

Genotype–phenotype correlations in laminopathies: how does fate translate?

2010 ◽  
Vol 38 (1) ◽  
pp. 257-262 ◽  
Author(s):  
Juergen Scharner ◽  
Viola F. Gnocchi ◽  
Juliet A. Ellis ◽  
Peter S. Zammit
Keyword(s):  
Intermediate Filament ◽  
Clinical Condition ◽  
Lamin A ◽  
Lmna Gene ◽  
Intermediate Filament Proteins ◽  
Pathogenic Mechanisms ◽  
Lmna Mutation ◽  
Disease Penetrance ◽  
Recent Developments ◽  
Different Tissues

A-type laminopathies are a group of diseases resulting from mutations in the intermediate filament proteins lamin A and C (both encoded by the LMNA gene), but for which the pathogenic mechanisms are little understood. In some laminopathies, there is a good correlation between the presence of a specific LMNA mutation and the disease diagnosed. In others however, many different mutations can give rise to the same clinical condition, even though the mutations may be distributed throughout one, or more, of the three functionally distinct protein domains of lamin A/C. Conversely, certain mutations can cause multiple laminopathies, with related patients carrying an identical mutation even having separate diseases, often affecting different tissues. Therefore clarifying genotype–phenotype links may provide important insights into both disease penetrance and mechanism. In the present paper, we review recent developments in genotype–phenotype correlations in laminopathies and discuss the factors that could influence pathology.

scholarly journals Expression of nuclear lamins in mammalian somatic cells lacking cytoplasmic intermediate filament proteins

1989 ◽  
Vol 92 (3) ◽  
pp. 361-370 ◽  
Author(s):  
M. Paulin-Levasseur ◽  
A. Scherbarth ◽  
G. Giese ◽  
K. Roser ◽  
W. Bohn ◽  
...  
Keyword(s):  
Cell Lines ◽  
Phorbol Ester ◽  
Intermediate Filament ◽  
Mammalian Cells ◽  
Somatic Cells ◽  
Nuclear Lamina ◽  
Intermediate Filament Proteins ◽  
Inhibition Of Proliferation ◽  
Lamin B ◽  
Nuclear Lamins

Using immunofluorescence and immunoblotting techniques, we have examined the composition of the nuclear lamina in murine plasmacytoma cells, MPC-11, exposed to the phorbol ester TPA as well as in two cell lines devoid of cytoplasmic intermediate filament proteins, the human adrenal cortex carcinoma-derived cells SW-13 and the clone C6-M-D4 derived from the rat glial cell line C6. Our results show that the inhibition of proliferation and the induction of vimentin synthesis observed in TPA-treated MPC-11 populations are not paralleled by changes in the lamin complement of these cells, which contain lamin B but lack lamins A and C. Furthermore, the analysis performed on SW-13 and C6-M-D4 cell lines clearly demonstrates that mammalian somatic cells display considerable variations in lamin expression and indicates that lamin B may be the only lamin species constitutively expressed in mammalian cells.

scholarly journals Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins

2021 ◽  
Vol 22 (8) ◽  
pp. 4256
Author(s):  
Lorenzo Maggi ◽  
Manolis Mavroidis ◽  
Stelios Psarras ◽  
Yassemi Capetanaki ◽  
Giovanna Lattanzi
Keyword(s):  
Muscular Dystrophy ◽  
Cardiac Muscle ◽  
Intermediate Filament ◽  
Striated Muscle ◽  
Congenital Muscular Dystrophy ◽  
Left Ventricular ◽  
Intermediate Filament Proteins ◽  
Muscle Disorders ◽  
Genes Encoding ◽  
Molecular Aspects

Intermediate filaments are major components of the cytoskeleton. Desmin and synemin, cytoplasmic intermediate filament proteins and A-type lamins, nuclear intermediate filament proteins, play key roles in skeletal and cardiac muscle. Desmin, encoded by the DES gene (OMIM *125660) and A-type lamins by the LMNA gene (OMIM *150330), have been involved in striated muscle disorders. Diseases include desmin-related myopathy and cardiomyopathy (desminopathy), which can be manifested with dilated, restrictive, hypertrophic, arrhythmogenic, or even left ventricular non-compaction cardiomyopathy, Emery–Dreifuss Muscular Dystrophy (EDMD2 and EDMD3, due to LMNA mutations), LMNA-related congenital Muscular Dystrophy (L-CMD) and LMNA-linked dilated cardiomyopathy with conduction system defects (CMD1A). Recently, mutations in synemin (SYNM gene, OMIM *606087) have been linked to cardiomyopathy. This review will summarize clinical and molecular aspects of desmin-, lamin- and synemin-related striated muscle disorders with focus on LMNA and DES-associated clinical entities and will suggest pathogenetic hypotheses based on the interplay of desmin and lamin A/C. In healthy muscle, such interplay is responsible for the involvement of this network in mechanosignaling, nuclear positioning and mitochondrial homeostasis, while in disease it is disturbed, leading to myocyte death and activation of inflammation and the associated secretome alterations.

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