The roles of the microtubule cytoskeletal network in cardiac mechanobiology

Fig. 1. Cytoskeletal structures associated with cardiomyocyte mechanobiology. (A) Intracellular cardiomyocyte structures involved in mechanotransduction pathways. Microtubules are anchored to desmins at the Z-discs of sarcomeres and form a cage surrounding the nucleus. Lamins form a dense network on the inner surface of the nuclear envelope. (B) Transmembrane mechanotransduction receptors. PIEZO1 and other tension-mediated ion channels control the influx and efflux of particles that regulate cardiomyocyte contraction. Adhesion junctions, such as integrins at costameres, provide mechanosensation of the surrounding ECM. The intermediate filament desmin links to the costamere and forms a network connecting Z-discs of adjacent myofibrils. (C) Intercalated disc junctions that attach cardiomyocytes to provide electro-mechanical coupling and allow cardiac tissue to function as one continuum. These junctions are composed of adherens junctions, desmosomes and gap junctions. Created in BioRender by Murphy, J., 2026. https://BioRender.com/5uiseci. This figure was sublicensed under CC-BY 4.0 terms.

Fig. 2. Structural components for mechanosensing in a mature cardiomyocyte. (A) Sarcomere shortening. Actin–myosin motor interactions shorten sarcomere units, thus causing hierarchical shortening at the cell and tissue level. (B) Titin elasticity. The elastic titin spring provides passive tension to resist overstretching of the sarcomere. (C) Transmembrane force transmission. Integrins and other adhesion complexes relay tensile signals intracellularly from the extracellular matrix. (D) Mechanosensitive ion channels. Tension-mediated ion channels regulate cardiomyocyte contraction through controlling Ca2+ tropomyosin binding and regulation of action potential. (E) Perinuclear microtubule cage. A dense microtubule network surrounds the nucleus, shielding it from mechanical loads and redistributing forces throughout the cell. (F) Microtubule buckling. Microtubules anchored at Z-discs undergo buckling during contraction. This buckling opposes sarcomere contraction and elongation, providing structural rigidity and a restoring force toward the relaxed length. Created in BioRender by Murphy, J., 2026. https://BioRender.com/5uiseci. This figure was sublicensed under CC-BY 4.0 terms.