The tethering of chromatin to the nuclear envelope supports nuclear mechanics

Abstract

The nuclear lamina is thought to be the primary mechanical defence of the nucleus. However, the lamina is integrated within a network of lipids, proteins and chromatin; the interdependence of this network poses a challenge to defining the individual mechanical contributions of these components. Here, we isolate the role of chromatin in nuclear mechanics by using a system lacking lamins. Using novel imaging analyses, we observe that untethering chromatin from the inner nuclear membrane results in highly deformable nuclei in vivo, particularly in response to cytoskeletal forces. Using optical tweezers, we find that isolated nuclei lacking inner nuclear membrane tethers are less stiff than wild-type nuclei and exhibit increased chromatin flow, particularly in frequency ranges that recapitulate the kinetics of cytoskeletal dynamics. We suggest that modulating chromatin flow can define both transient and long-lived changes in nuclear shape that are biologically important and may be altered in disease.

Nuclear morphologies: their diversity and functional relevance

“…Schreiner et al 2015) with high-throughput techniques such as chromosome conformation capture and its variants, in which chromatin structure can be reconstructed by sequencing and mapping physically adjacent regions of DNA. Although chromosome conformation capture has the limitation of operating at the scale of millions of cells, and averages out subtle differences between individual cells, it has demonstrated clear and reproducible differences between cell types (Pueschel et al 2016).…”

“…Recent work by Schreiner et al (2015) in the fission yeast Schizosaccharomyces pombe showed the effect of chromatin flow on the rigidity of the nucleus. S.pombe lacks lamins, and thus has a flexible nucleus which can be studied outside the influence of the lamin proteins.…”

“…S.pombe lacks lamins, and thus has a flexible nucleus which can be studied outside the influence of the lamin proteins. Schreiner et al (2015) found that the degree of tethering of chromatin by LINC complex proteins to the inner nuclear membrane affected the stiffness of the nucleus against microtubule-induced deformations.…”

Biophysical studies of cholesterol effects on chromatin

“…In addition, the tethering of chromatin to the nuclear periphery has an important role in the chromatin flow by defining changes in nuclear shape (34). We could raise the hypothesis that cholesterol might trigger chromatin structural changes that may contribute to the intra-nuclear organization of chromatin.…”

Megan King: A force to be reckoned with

“…In addition, it houses the chromosomes, which behave very differently from other macromolecular complexes due to the sheer size of the chromatin polymer. These different attributes make the nucleus very interesting from its basic biophysical properties on up (4). I then became fascinated with understanding why the nuclear envelope doesn’t simply tubulate in response to cytoskeletal forces (like the ER does).…”