In Situ Mechanotransduction Via Vinculin Regulates Stem Cell Differentiation

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2013 Jul 31

PMID 23897765

Citations 49

Authors

Andrew W Holle

Xinyi Tang

Deepthi Vijayraghavan

Ludovic G Vincent

Alexander Fuhrmann

Yu Suk Choi

Juan C Del Alamo

Adam J Engler

Affiliations

Soon will be listed here.

Abstract

Human mesenchymal stem cell (hMSC) proliferation, migration, and differentiation have all been linked to extracellular matrix stiffness, yet the signaling pathway(s) that are necessary for mechanotransduction remain unproven. Vinculin has been implicated as a mechanosensor in vitro, but here we demonstrate its ability to also regulate stem cell behavior, including hMSC differentiation. RNA interference-mediated vinculin knockdown significantly decreased stiffness-induced MyoD, a muscle transcription factor, but not Runx2, an osteoblast transcription factor, and impaired stiffness-mediated migration. A kinase binding accessibility screen predicted a cryptic MAPK1 signaling site in vinculin which could regulate these behaviors. Indeed, reintroduction of vinculin domains into knocked down cells indicated that MAPK1 binding site-containing vinculin constructs were necessary for hMSC expression of MyoD. Vinculin knockdown does not appear to interfere with focal adhesion assembly, significantly alter adhesive properties, or diminish cell traction force generation, indicating that its knockdown only adversely affected MAPK1 signaling. These data provide some of the first evidence that a force-sensitive adhesion protein can regulate stem cell fate.

Citing Articles

Focal Adhesion's Role in Cardiomyocytes Function: From Cardiomyogenesis to Mechanotransduction.

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Vinculin is essential for sustaining normal levels of endogenous forces at cell-cell contacts.

Mezher M, Dumbali S, Fenn I, Lamb C, Miller C, Sharmin S Biophys J. 2024; 122(23):4518-4527.

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