title: Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension.
abstract: Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.|NeuroGroup, BioMediTech, University of Tampere, Tampere, Finland.
authors: Teemu O
authors: TO
authors: Ihalainen
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
authors: Lina
authors: L
authors: Aires
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
authors: Florian A
authors: FA
authors: Herzog
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
authors: Ruth
authors: R
authors: Schwartlander
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
authors: Jens
authors: J
authors: Moeller
authors: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
authors: Viola
authors: V
authors: Vogel
mesh_terms: D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry / Q000378:metabolism*; D034881:Nuclear Lamina / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D001704:Biopolymers; C494847:LMNA protein, human; D034904:Lamin Type A