Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation
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,Dennis E. Discher +13 more
TLDR
In this article, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, as did levels of collagens in the extracellular matrix that determine E.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.read more
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Hydrogels with tunable stress relaxation regulate stem cell fate and activity
Ovijit Chaudhuri,Ovijit Chaudhuri,Ovijit Chaudhuri,Luo Gu,Luo Gu,Darinka D. Klumpers,Darinka D. Klumpers,Darinka D. Klumpers,Max Darnell,Max Darnell,Sidi A. Bencherif,Sidi A. Bencherif,James C. Weaver,Nathaniel Huebsch,Hong-pyo Lee,Evi Lippens,Evi Lippens,Georg N. Duda,David J. Mooney,David J. Mooney +19 more
TL;DR: It is found that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation, highlighting stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.
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TL;DR: The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.
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Mechanical forces direct stem cell behaviour in development and regeneration
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Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores
Alberto Elosegui-Artola,Ion Andreu,Ion Andreu,Amy E. M. Beedle,Amy E. M. Beedle,Ainhoa Lezamiz,Ainhoa Lezamiz,Marina Uroz,Anita Joanna Kosmalska,Roger Oria,Jenny Z. Kechagia,Palma Rico-Lastres,Palma Rico-Lastres,Anabel-Lise Le Roux,Catherine M. Shanahan,Xavier Trepat,Daniel Navajas,Sergi Garcia-Manyes,Sergi Garcia-Manyes,Pere Roca-Cusachs +19 more
TL;DR: This work shows that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport, demonstrated for YAP but with potential general applicability in transcriptional regulation.
References
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