Abstract
ABSTRACTWhile diverse cellular components have been identified as mechanotransduction elements, the deformation of the nucleus itself is a critical mechanosensory mechanism, implying that nuclear stiffness is essential in determining responses to intracellular and extracellular stresses. Although the nuclear membrane protein lamin A/C is known to contribute to nuclear stiffness, bulk moduli of nuclei have not been reported for various levels of lamin A/C. Here, we measure the nuclear bulk moduli as a function of lamin A/C expression and applied osmotic stress, revealing a linear dependence within the range of 2–4 MPa. We also find that the nuclear compression is anisotropic, with the vertical axis of the nucleus being more compliant than the minor and major axes in the substrate plane. We then related the spatial distribution of lamin A/C with submicron 3D nuclear envelope deformation, revealing that local areas of the nuclear envelope with higher density of lamin A/C have correspondingly lower local deformations. These findings describe the complex dispersion of nuclear deformations as a function of lamin A/C expression and distribution, implicating a lamin A/C role in mechanotransduction.This article has an associated First Person interview with the first author of the paper.
Highlights
The nucleus is one of the most crucial organelles and the storehouse of DNA in the cell, integrating diverse biochemical cues for proper cell function (Lamond and Earnshaw, 1998)
Though the nuclear membrane protein lamin A/C is known to contribute to nuclear stiffness, bulk moduli of nuclei have not been reported for various levels of lamin A/C
The nucleus is notably stiffer than the cytoplasm (0.5-3kPa) (Chen et al, 2012), with an effective Young’s modulus ranging from 1–10kPa (Caille et al, 2002; Vaziri and Mofrad, 2007); while these values appear relatively consistent in a given cell line (Adele Khavari, 2019), multiple factors may cause nuclear stiffness to change significantly
Summary
The nucleus is one of the most crucial organelles and the storehouse of DNA in the cell, integrating diverse biochemical cues for proper cell function (Lamond and Earnshaw, 1998). To understand the quantitative impact of lamin A/C structure on nuclear mechanics, here we measure the deformability and bulk moduli of nuclei as a function of lamin A/C expression.
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