Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

24-POS Board 24 Mechanical Tension Regulates C-Terminus Accessibility of Lamin A/C Teemu O. Ihalainen 1,2 , Lina Aires 2 , Florian A. Herzog 2 , Ruth Schwartlander 2 , Jens Moeller 2 , Viola Vogel 2 . 1 University of Tampere, Tampere, Finland, 2 ETH Zurich, Zurich, Switzerland. Cells exploit traction forces to sense the physical characteristics of their microenvironments, which co-regulates a variety of cellular processes. Mechanical forces, rising from the extracellular environment or from the contractile cell cytoskeleton, can be transmitted to the nucleus as the cytoskeleton physically couples the cell periphery to the nuclear envelope. Nuclear lamina plays a key role in the nuclear mechanotransduction, since it resides in the interface between the cytoplasm and the inner nucleus. The nuclear lamina is composed of a 10– 60 nm thick protein layer beneath the inner nuclear membrane and its major constituents are A- and B-type lamins. A-type lamins (lamin A, AΔ10, C) are splice variants of a single gene, LMNA, whereas B-type lamins are encoded from two different genes LMNB1 (lamin B1) and LMNB2(lamin B2, B3). Lamins are involved in the regulation of gene expression and control the mechanical stability of the nucleus. However, relatively little is known about mechanoregulation and mechanosensitivity of lamin proteins Here, we show that at least two N- and C-terminal regions of lamin A/C are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. 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-cap assembly. Notably, the identified region in the C-terminus of lamin A/C overlaps with emerin, DNA and histone binding sites, and contains various laminopathy mutation sites. Our findings help to decipher how the physical properties of cellular microenvironments can regulate nuclear events and gene expression via altered lamin A/C structure.

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