Mechanics of the Nucleus

Abstract

The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information of the cell and associated machinery, without much attention to its structure and mechanical properties. This article provides compelling examples that illustrate how specific nuclear structures are associated with important cellular functions, and how defects in nuclear mechanics can cause a multitude of human diseases. During differentiation, embryonic stem cells modify their nuclear envelope composition and chromatin structure, resulting in stiffer nuclei that reflect decreased transcriptional plasticity. In contrast, neutrophils have evolved characteristic lobulated nuclei that increase their physical plasticity, enabling passage through narrow tissue spaces in their response to inflammation. Research on diverse cell types further demonstrates how induced nuclear deformations during cellular compression or stretch can modulate cellular function. Pathological examples of disturbed nuclear mechanics include the many diseases caused by mutations in the nuclear envelope proteins lamin A/C and associated proteins, as well as cancer cells that are often characterized by abnormal nuclear morphology. In this article, we will focus on determining the functional relationship between nuclear mechanics and cellular (dys-)function, describing the molecular changes associated with physiological and pathological examples, the resulting defects in nuclear mechanics, and the effects on cellular function. New insights into the close relationship between nuclear mechanics and cellular organization and function will yield a better understanding of normal biology and will offer new clues into therapeutic approaches to the various diseases associated with defective nuclear mechanics.

The living aortic valve: From molecules to function

“…The nucleus, however, is mechanically connected to the cytoplasm and deforms as the cell deforms, supporting the observation that transcriptional activity can be affected rapidly 140 . Recent studies have identified a class of nuclear membrane proteins called lamins that are mechanosensitive and involved in a number of clinical conditions, including progeria and cancer 141 . Recently, we stretched mouse valve leaflets ex vivo and followed local cell and matrix fiber deformations in combination with global tissue stretch 142 .…”

Squish and squeeze — the nucleus as a physical barrier during migration in confined environments

“…The nucleus is the largest organelle in the cell, with a diameter between 3–15 µm [11,12], making it substantially larger than many pores encountered during migration in physiological tissues. Furthermore, biophysical measurements of isolated nuclei and intact cells reveal that the nucleus is typically 2- to 10-times stiffer than the surrounding cytoplasm [11].…”

“…Furthermore, biophysical measurements of isolated nuclei and intact cells reveal that the nucleus is typically 2- to 10-times stiffer than the surrounding cytoplasm [11]. This combination of large size and relative rigidity of the nucleus led to the hypothesis that the nucleus can impact the cells’ ability to migrate [13].…”

Brillouin flow cytometry for label-free mechanical phenotyping of the nucleus

“…Currently, extracting mechanical properties of the nucleus requires staining, along with additional information and assumptions about how forces are transmitted within a cell. For pristine mechanical information, the nucleus has to be isolated to allow AFM or micropipette measurement, which makes the procedure not suitable for microfluidic platforms 17 .…”