Viscoelastic behavior of cardiomyocytes carrying LMNA mutations

BACKGROUND: Laminopathies are genetic diseases caused by mutations in the nuclear lamina. OBJECTIVE: Given the clinical impact of laminopathies, understanding mechanical properties of cells bearing lamin mutations will lead to advancement in the treatment of heart failure. METHODS: Atomic force microscopy (AFM) was used to analyze the viscoelastic behavior of neonatal rat ventricular myocyte cells expressing three human lamin A/C gene (LMNA) mutations. RESULTS: Cell storage modulus is characterized, by two plateaus, one in the low frequency range, a second one at higher frequencies. The loss modulus instead shows a “bell” shape with a relaxation toward fluid properties at lower frequencies. Mutations shift the relaxation to higher frequencies, rendering the networks more solid-like. Is interesting that this increase of mutations stiffness (solid like behavior) is at frequencies around 1 Hz, close to the human heart rate. CONCLUSIONS: These features result from a combination of the properties of cytoskeleton filaments and their temporary cross-linker. Our results substantiate that cross-linked filaments contribute for the most part of the mechanical strength of the cytoskeleton cell studied and the relaxation time is determined by the dissociation dynamics of the cross-linking proteins. The severity of biomechanical defects due to these LMNA mutations correlated with the severity of the clinical phenotype.