Nanohelical Shape and Periodicity Dictate Stem Cell Fate in a Synthetic Matrix

Abstract

Several aspects of the extracellular matrix (ECM) microenvironment, such as protein composition, topographical features and elasticity, have been reported to play critical roles in stem cell lineage specification. In vivo, the ECM is composed of nano-fibrillar networks of defined periodicity. Changes in the periodicity and shape of this nanofiber matrix have been implicated in the induction of several diseases. Despite this, till date, there has been no investigation of the effect of the nanoperiodicity of the ECM nanostructure on the fate of stem cells. In this report, we use helical organic nanoribbons based on self-assembled Gemini amphiphiles to access chiral silica nanoribbons with different shapes (twisted/helical) and periodicity. Glass substrates covalently grafted with ‘RGD’ functionalized helical nanoribbons of periodicity 63 nm induced specific hMSC adhesion through fibrillar focal contact formation, and commitment towards osteoblast lineage in absence of osteogenic-inducing media. In contrast, the substrate with twisted nanoribbons of periodicity 100 nm failed to induce osteogenic commitment. Inhibition of non-muscle myosin II with blebbistatin was sufficient to block osteogenic commitment on helical nanoribbon matrix, demonstrating that the stem cells interpreted nanohelical shape and periodicity environment in the same way they sense microenvironment elasticity. This study thus provides a promising tool to promote osteogenic capacity and may find applications in bone tissue engineering. silica nanostructures, nanohelical periodicity, stem cell microenvironment, cell differentiation.