Defective Biomechanics and Pharmacological Rescue of Human Cardiomyocytes with Filamin C Truncations.

ABSTRACT: Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants (FLNCtv) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, we investigated the mechanical properties of human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) carrying FLNCtv. CRISPR/Cas9 genome-edited homozygous FLNC^KO-/- hiPSC-CMs and heterozygous knock-out FLNC^KO+/- hiPSC-CMs were analyzed and compared to wild-type FLNC (FLNC^WT) hiPSC-CMs. Atomic force microscopy (AFM) was used to perform micro-indentation to evaluate passive and dynamic mechanical properties. A qualitative a

SUBMITTER: Lazzarino M 

PROVIDER: S-EPMC10932268 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature