Given the clinical effect of laminopathies, understanding lamin mechanical properties will benefit the treatment
of heart failure. Here we report a mechano-dynamic study of LMNA mutations in neonatal rat ventricular myocytes
(NRVM) using single cell spectroscopy with Atomic Force Microscopy (AFM) and measured changes in
beating force, frequency and contractile amplitude of selected mutant-expressing cells within cell clusters.
Furthermore, since beat-to-beat variations can provide clues on the origin of arrhythmias, we analyzed the beating
rate variability using a time-domain method which provides a Poincare plot. Data were further correlated to cell
phenotypes. Immunofluorescence and calcium imaging analysis showed that mutant lamin changed NRVMs
beating force and frequency. Additionally, we noted an altered microtubule network organization with shorter
filament length, and defective hemichannel membrane localization (Connexin 43). These data highlight the
interconnection between nucleoskeleton, cytoskeleton and sarcolemmal structures, and the transcellular consequences
of mutant lamin protein in the pathogenesis of the cardiac laminopathies
