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A close-up view of cardiac cell mechanics Heart cells contain a very well-organized array of cytoskeletal elements, including actin and microtubules that help them to perform their mechanical functions. Robison et al. used an advanced imaging approach to study the inner workings of mouse cardiac myocytes in real time. They observed microtubule “buckling” under contractile force in beating cardiomyocytes. This buckling was regulated by interaction with desmin and by the tubulin tyrosination state. The findings suggest a role for stable detyrosinated microtubules whose buckling under tension contributes to cardiac muscle strength. Science , this issue p. 10.1126/science.aaf0659

The heart is the first organ to develop in vertebrate embryos, and coordinated beating of cardiomyocytes is likely facilitated by structural proteins of the extracellular matrix, cytoskeleton, and even the nucleus. We first show that the nucleus beats in the intact embryonic heart and that nuclear beating in vitro is regulated by matrix stiffness. However, it has been unclear when the nuclear structural protein Lamin-A turns on, which seems important because Lmna knockout mice are known to exhibit ‘developmental defects of the heart’ and die shortly after birth. We show that nuclear lamin levels parallel the development of mechanical stiffness and stress in normal embryos. While early embryos are well-known to be uniformly soft, our measurements using a chick embryo model show that the heart begins to stiffen almost immediately following initial differentiation, with tissue stiffness E of 1-2 kPa at embryonic day 4 (E4) increasing significantly by E6. This is accompanied by an increase in Lamin-A levels and comparatively constant Lamin-B expression, with Lamin-A:B stoichiometry already known to function as a mechanosensor in adult tissue [Swift, Science 2013]. Proteomic analyses of lamins from E4 to E10 indeed show that Lamin-A:B stoichiometry scales with stiffness as measured for adult tissue. Inhibition of actomyosin with blebbistatin reversibly reduces beating and contractility of isolated E4 hearts, leading to lower cytoskeletal tension and changes in lamin levels. Isolated cardiomyocytes beat optimally on gels that match the stiffness of embryonic hearts and nuclear beating follows the same trend, with ongoing studies focused on lamin responsiveness including phosphorylation and transcriptional regulation. Nuclear lamins are thus embryonic stress sensors that mechanically link to the cytoskeleton and the matrix, potentially feeding back to cytoskeletal maturation in differentiation.