Bifunctional Hydrogels Containing the Laminin Motif IKVAV PromoteNeurogenesis.

Aleeza Farrukh,Benedikt Berninger,Marcelo J Salierno,Nicolás Marichal,Julieta I Paez,Wenqiang Fan,Aránzazu Del Campo,Felipe Ortega

doi:10.1016/j.stemcr.2017.09.002

Abstract

SummaryEngineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing β1-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties.

Highlights

There is a surge of interest in designing hydrogels endowed with specific mechanical and chemical properties for steering cell behavior, including cell-fate decision and plasticity as well as organoid formation (Engler et al, 2006; Floren et al, 2016; Gjorevski et al, 2016; Her et al, 2013; Wen et al, 2014)
We address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes
While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing b1-integrin in embryonic cortical neurons

Summary

Introduction

There is a surge of interest in designing hydrogels endowed with specific mechanical and chemical properties for steering cell behavior, including cell-fate decision and plasticity as well as organoid formation (Engler et al, 2006; Floren et al, 2016; Gjorevski et al, 2016; Her et al, 2013; Wen et al, 2014). We have studied lineage progression of neural stem cells (NSCs) from the adult subependymal zone (SEZ) using hard surfaces coated with polylysine (Costa et al, 2011; Ortega et al, 2011), leaving the question open whether the observed patterns of cell division and terminal differentiation within single clones can be altered by modifying the mechanical and chemical properties of the substrate. One component shown to regulate the activated state of adult SEZ NSCs is the basement membrane glycoprotein laminin (Kokovay et al, 2010). IKVAV was found to enhance viability and maturation of neurons by binding to the b1-integrin subunit (Agius et al, 1996; Li et al, 2014; Sur et al, 2012; Tashiro et al, 1989), rendering it a promising candidate for use in neuronal growth-stimulating materials

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