Image‐Based Elastography of Heterochromatin and Euchromatin Domains in the Deforming Cell Nucleus. Issue 5 (15th January 2021)

• Record Type: Journal Article
• Authors: Ghosh, Soham; Cuevas, Victor Crespo; Seelbinder, Benjamin; Neu, Corey P.
• Is Part Of: Small. Volume 17:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-01-15
• Subjects: chromatin -- inverse methods -- LINC complex -- mechanobiology -- nuclear mechanics; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202006109
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Chromatin of the eukaryotic cell nucleus comprises microscopically dense heterochromatin and loose euchromatin domains, each with distinct transcriptional ability and roles in cellular mechanotransduction. While recent methods are developed to characterize the mechanics of nucleus, measurement of intranuclear mechanics remains largely unknown. Here, the development of "nuclear elastography, " which combines microscopic imaging and computational modeling to quantify the relative elasticity of the heterochromatin and euchromatin domains, is described. Using contracting murine embryonic cardiomyocytes, nuclear elastography reveals that the heterochromatin is almost four times stiffer than the euchromatin at peak deformation. The relative elasticity between the two domains changes rapidly during the active deformation of the cardiomyocyte in the normal physiological condition but progresses more slowly in cells cultured in a mechanically stiff environment, although the relative stiffness at peak deformation does not change. Further, it is found that the disruption of the Klarsicht, ANC‐1, Syne Homology domain of the Linker of Nucleoskeleton and Cytoskeleton complex compromises the intranuclear elasticity distribution resulting in elastically similar heterochromatin and euchromatin. These results provide insight into the elastography dynamics of heterochromatin and euchromatin domains and provide a noninvasive framework to further investigate the mechanobiological function of subcellular and subnuclear domains limited only by the spatiotemporal resolution of the acquired images. Abstract : Optical microscopy, image analysis, and computational modeling are used in combination to investigate intranuclear elastography. Relative stiffness of euchromatin and heterochromatin domains is quantified noninvasively. Compared to a soft mechanical environment, on a stiff substrate, the dynamics of nuclear elastography is altered. Nuclear envelope protein disruption affects the relative stiffness of the intranuclear space.