Components and Mechanisms of Nuclear Mechanotransduction

Abstract

The cell nucleus is best known as the container of the genome. Its envelope provides a barrier for passive macromolecule diffusion, which enhances the control of gene expression. As its largest and stiffest organelle, the nucleus also defines the minimal space requirements of a cell. Internal or external pressures that deform a cell to its physical limits cause a corresponding nuclear deformation. Evidence is consolidating that the nucleus, in addition to its genetic functions, serves as a physical sensing device for critical cell body deformation. Nuclear mechanotransduction allows cells to adapt their acute behaviors, mechanical stability, paracrine signaling, and fate to their physical surroundings. This review summarizes the basic chemical and mechanical properties of nuclear components, and how these properties are thought to be utilized for mechanosensing.

Keywords: chromatin; lamina; laminopathy; mechanotransduction; nuclear membrane; nucleus; progeria.

Figure 1

Components of nuclear mechanotransduction. Schematic overview (left panel) and zoomed-in section of the nuclear envelope (left panel, black box & right panel), with INM and ONM, chromatin (turquoise and gray), and the nuclear lamina (yellow and purple). LADs and the LINC are depicted in the zoomed-in view. Nuclear pore complexes (blue), the endoplasmic reticulum, and the invaginations of the nucleoplasmic reticulum are depicted in the overview panel. Abbreviations: BAF, barrier-to-autointegration factor; F-actin, fibrous actin; INM, inner nuclear membrane; LAD, lamina-associated domain; LINC, linker of nucleoskeleton and cytoskeleton complex; ONM, outer nuclear membrane; ER, endoplasmic reticulum; NR, nucleoplasmic reticulum; P, phosphorylated; SUN-1/2, Sad1p/UNC-84 1/2.

Figure 2

Mechanisms of nuclear mechanotransduction. (A) Molecular level: Deformation of the nucleus causes subnanometer structural changes in the NM lipid bilayers, integral NM proteins (channel- & pore-proteins), chromatin, lamins, and other deformable molecular complexes (conceptualized by boxes connected with lines) that unmask new interaction sites (void between boxes) and change NM permeability to ions and proteins (black dots). Binding/activation of enzymes and transcription factors (blue shapes) convert these structural changes into chemical signals (red stars). (B) Cellular level: the structural changes in nuclear components promote the redistribution of transcriptional regulators (green) between the cyto- and nucleoplasm, and lipid enzymes (blue shapes) between the nucleoplasm and the NM, as well as the efflux of Ca²⁺ (black sprinkles) from the endoplasmic reticulum through MSCs. For simplicity, protein redistribution within the NM and to chromatin is not depicted in this scheme. Red lines, contractile actomyosin fibers. Black circles, focal adhesions and LINC complexes. Abbreviations: NM, nuclear membrane; MSCs, mechanosensitive ion channels.