N-cadherin Adhesive Interactions Modulate Matrix Mechanosensing and Fate Commitment of Mesenchymal Stem Cells

Overview

Journal Nat Mater

Date 2016 Aug 16

PMID 27525568

Citations 128

Authors

Brian D Cosgrove

Keeley L Mui

Tristan P Driscoll

Steven R Caliari

Kush D Mehta

Richard K Assoian

Jason A Burdick

Robert L Mauck

Affiliations

Soon will be listed here.

Abstract

During mesenchymal development, the microenvironment gradually transitions from one that is rich in cell-cell interactions to one that is dominated by cell-ECM (extracellular matrix) interactions. Because these cues cannot readily be decoupled in vitro or in vivo, how they converge to regulate mesenchymal stem cell (MSC) mechanosensing is not fully understood. Here, we show that a hyaluronic acid hydrogel system enables, across a physiological range of ECM stiffness, the independent co-presentation of the HAVDI adhesive motif from the EC1 domain of N-cadherin and the RGD adhesive motif from fibronectin. Decoupled presentation of these cues revealed that HAVDI ligation (at constant RGD ligation) reduced the contractile state and thereby nuclear YAP/TAZ localization in MSCs, resulting in altered interpretation of ECM stiffness and subsequent changes in downstream cell proliferation and differentiation. Our findings reveal that, in an evolving developmental context, HAVDI/N-cadherin interactions can alter stem cell perception of the stiffening extracellular microenvironment.

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