Lamins A and C but not lamin B1 regulate nuclear mechanics.
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.
Lammerding
Jan
J
Cardiovascular Division, Department of Medicine, and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02139, USA. jlammerding@rics.bwh.harvard.edu
Fong
Loren G
LG
Ji
Julie Y
JY
Reue
Karen
K
Stewart
Colin L
CL
Young
Stephen G
SG
Lee
Richard T
RT
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D003433:Crosses, Genetic; D006579:Heterozygote; D034904:Lamin Type A / Q000737:chemistry* / Q000502:physiology; D034921:Lamin Type B / Q000737:chemistry* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009685:Nuclear Envelope / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D034904:Lamin Type A; D034921:Lamin Type B; D011993:Recombinant Fusion Proteins; C440308:lamin C