Jump to main content
Jump to site search

Issue 32, 2015
Previous Article Next Article

Nuclear stiffening and chromatin softening with progerin expression leads to an attenuated nuclear response to force

Author affiliations

Abstract

Progerin is a mutant form of the nucleoskeletal protein lamin A, and its expression results in the rare premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). Patients with HGPS demonstrate several characteristic signs of aging including cardiovascular and skeletal dysfunction. Cells from HGPS patients show several nuclear abnormalities including aberrant morphology, nuclear stiffening and loss of epigenetic modifications including heterochromatin territories. However, it is unclear why these changes disproportionately impact mechanically-responsive tissues. Using micropipette aspiration, we show that nuclei in progerin-expressing cells are stiffer than control cells. Conversely, our particle tracking reveals the nuclear interior becomes more compliant in cells from HGPS patients or with progerin expression, as consistent with decreased chromatin condensation as shown previously. Additionally, we find the nuclear interior is less responsive to external mechanical force from shear or compression likely resulting from damped force propagation due to nucleoskeletal stiffening. Collectively our findings suggest that force is similarly transduced into the nuclear interior in normal cells. In HGPS cells a combination of a stiffened nucleoskeleton and softened nuclear interior leads to mechanical irregularities and dysfunction of mechanoresponsive tissues in HGPS patients.

Graphical abstract: Nuclear stiffening and chromatin softening with progerin expression leads to an attenuated nuclear response to force

Back to tab navigation

Supplementary files

Publication details

The article was received on 08 Mar 2015, accepted on 06 Jul 2015 and first published on 14 Jul 2015


Article type: Paper
DOI: 10.1039/C5SM00521C
Author version
available:
Download author version (PDF)
Citation: Soft Matter, 2015,11, 6412-6418
  •   Request permissions

    Nuclear stiffening and chromatin softening with progerin expression leads to an attenuated nuclear response to force

    E. A. Booth, S. T. Spagnol, T. A. Alcoser and K. N. Dahl, Soft Matter, 2015, 11, 6412
    DOI: 10.1039/C5SM00521C

Search articles by author

Spotlight

Advertisements