Lamins A and C but Not Lamin B1 Regulate Nuclear Mechanics

TLDR

Mutations in lamins A and C cause diverse diseases, and their loss reduces nuclear stiffness and increases fragility, leading to cell death under mechanical strain. The study aimed to determine how lamins A, C, and B1 contribute to nuclear mechanics by assessing shape, dynamics, deformation, and viability under strain in cells lacking each lamin. Researchers analyzed nuclear shape, dynamics over time, deformations under strain, and cell viability in cells lacking both lamins A and C, cells lacking only lamin A (lamin C‑only), cells lacking wild‑type lamin B1, and wild‑type cells. Lamin A/C deficiency caused misshapen nuclei, severely reduced stiffness, and lower viability under strain, whereas lamin C‑only cells showed mild shape and stiffness changes without viability loss, and lamin B1 deficiency led to normal mechanics but increased blebbing, indicating that A and C drive nuclear stiffness while B1 maintains integrity.

Abstract

Mutations in the nuclear envelope proteins lamins A and C cause a broad variety of human diseases, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. Cells lacking lamins A and C have reduced nuclear stiffness and increased nuclear fragility, leading to increased cell death under mechanical strain and suggesting a potential mechanism for disease. Here, we investigated the contribution of major lamin subtypes (lamins A, C, and B1) to nuclear mechanics by analyzing nuclear shape, nuclear dynamics over time, nuclear deformations under strain, and cell viability under prolonged mechanical stimulation in cells lacking both lamins A and C, cells lacking only lamin A (i.e. "lamin C-only" cells), cells lacking wild-type lamin B1, and wild-type cells. Lamin A/C-deficient cells exhibited increased numbers of misshapen nuclei and had severely reduced nuclear stiffness and decreased cell viability under strain. Lamin C-only cells had slightly abnormal nuclear shape and mildly reduced nuclear stiffness but no decrease in cell viability under strain. Interestingly, lamin B1-deficient cells exhibited normal nuclear mechanics despite having a significantly increased frequency of nuclear blebs. Our study indicates that lamins A and C are important contributors to the mechanical stiffness of nuclei, whereas lamin B1 contributes to nuclear integrity but not stiffness.