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  • Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation.

Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation.

Science (New York, N.Y.) (2013-08-31)
Joe Swift, Irena L Ivanovska, Amnon Buxboim, Takamasa Harada, P C Dave P Dingal, Joel Pinter, J David Pajerowski, Kyle R Spinler, Jae-Won Shin, Manorama Tewari, Florian Rehfeldt, David W Speicher, Dennis E Discher
ABSTRACT

Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.

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