Biomechanical defects and rescue of cardiomyocytes expressing pathologic nuclear lamins

Given the clinical impact of LMNA cardiomyopathies, understanding lamin function will fulfill a clinical need and will lead to advancement in the treatment of heart failure. A multidisciplinary approach combining cell biology, atomic force microscopy (AFM) and molecular modeling was used to analyze the biomechanical properties of human lamin A/C gene (LMNA) mutations (E161K, D192G, N195K) using an in vitro neonatal rat ventricular myocyte (NRVM) model

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

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

Optimisation by Evolutionary Algorithms of Free-Layer Damping Treatments on Plates

2The problem of controlling or reducing vibration levels is very common in many different applications. From costly aeroplane fuselages to cheap domestic appliances the prob- lem can be tackled with the appropriate use of free layer damping treatments (FLDT).1 This technique, based on the distribution of layers of visoelastic material on the vibrating parts, is frequently adopted since it is cheap, efficient and easily applicable either at the design stage or in situ as a cor- rective measure. Due to these advantages and few limitations, not much care is taken to optimise the material distribution. Conversely, the necessity to produce lighter and quieter products will force the designer to optimise these treatments too. Under these circumstances, the most appropriate optimi- sation objectives seem to be the maximisation of the achiev- able damping levels and the minimisation of the amount of added material. In this work the potential of the genetic algorithm for the determination of thenonemixedBregant L.; Puzzi S.Bregant, Luigi; Puzzi, S