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The Cardiomyopathy Lamin A/C D192G Mutation Disrupts Whole-Cell Biomechanics in Cardiomyocytes as Measured by Atomic Force Microscopy Loading-Unloading Curve Analysis.

Lanzicher T, Martinelli V, Puzzi L, Del Favero G, Codan B, Long CS, Mestroni L, Taylor MR, Sbaizero O - Sci Rep (2015)

Bottom Line: Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls.Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein.These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering and Architecture, University of Trieste, Via Valerio 2, 34127, Trieste Italy.

ABSTRACT
Atomic force microscopy (AFM) cell loading/unloading curves were used to provide comprehensive insights into biomechanical behavior of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wall, myopathy and severe cardiomyopathy. Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls. Furthermore, there seems to be a connection between this lamin nuclear mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to-cell membrane adhesion. We believe that this loss of adhesion involves the cytoskeletal architecture since our microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the cytoskeleton. Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein. These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties.

No MeSH data available.


Related in: MedlinePlus

This cartoon shows a structure with dimples and the geometrical parameters used to calculate its bending stiffness.Our biomechanical data suggests that the LMNA D192G mutation may change the meshwork shape and therefore its mechanical properties.
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f6: This cartoon shows a structure with dimples and the geometrical parameters used to calculate its bending stiffness.Our biomechanical data suggests that the LMNA D192G mutation may change the meshwork shape and therefore its mechanical properties.

Mentions: where t = sheet thickness. In the case of a corrugated (dimpled) sheet (Fig. 6), the second moment of area is equal to:


The Cardiomyopathy Lamin A/C D192G Mutation Disrupts Whole-Cell Biomechanics in Cardiomyocytes as Measured by Atomic Force Microscopy Loading-Unloading Curve Analysis.

Lanzicher T, Martinelli V, Puzzi L, Del Favero G, Codan B, Long CS, Mestroni L, Taylor MR, Sbaizero O - Sci Rep (2015)

This cartoon shows a structure with dimples and the geometrical parameters used to calculate its bending stiffness.Our biomechanical data suggests that the LMNA D192G mutation may change the meshwork shape and therefore its mechanical properties.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555041&req=5

f6: This cartoon shows a structure with dimples and the geometrical parameters used to calculate its bending stiffness.Our biomechanical data suggests that the LMNA D192G mutation may change the meshwork shape and therefore its mechanical properties.
Mentions: where t = sheet thickness. In the case of a corrugated (dimpled) sheet (Fig. 6), the second moment of area is equal to:

Bottom Line: Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls.Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein.These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering and Architecture, University of Trieste, Via Valerio 2, 34127, Trieste Italy.

ABSTRACT
Atomic force microscopy (AFM) cell loading/unloading curves were used to provide comprehensive insights into biomechanical behavior of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wall, myopathy and severe cardiomyopathy. Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls. Furthermore, there seems to be a connection between this lamin nuclear mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to-cell membrane adhesion. We believe that this loss of adhesion involves the cytoskeletal architecture since our microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the cytoskeleton. Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein. These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties.

No MeSH data available.


Related in: MedlinePlus