Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers

Abstract

Neural progenitor cells were encapsulated in vitro within a three-dimensional network of nanofibers formed by self-assembly of peptide amphiphile molecules. The self-assembly is triggered by mixing cell suspensions in media with dilute aqueous solutions of the molecules, and cells survive the growth of the nanofibers around them. These nanofibers were designed to present to cells the neurite-promoting laminin epitope IKVAV at nearly van der Waals density. Relative to laminin or soluble peptide, the artificial nanofiber scaffold induced very rapid differentiation of cells into neurons, while discouraging the development of astrocytes. This rapid selective differentiation is linked to the amplification of bioactive epitope presentation to cells by the nanofibers.

Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage

“…Nanotopography has been demonstrated to enhance differentiation of progenitor cells into their programmed pathway [1,2]. Nevertheless, the novelty of this work lies in the application of nanotopography to direct adult stem cells to differentiate into a non-default pathway.…”

“…Topography of extracellular microenvironment can influence cellular responses from attachment and migration to differentiation and production of new tissue [1][2][3][4][5]. Cells in their natural environment interact with extracellular matrix (ECM) components in the nanometer scale [6].…”

Novel Nanomaterials for Clinical Neuroscience

“…Peptide nanofibers have been examined as potential neuronal scaffolds. In one study, nanofibers of self-assembling peptide molecules (IKVAV) were shown to promote and support neuronal regeneration (Silva et al 2004). In physiological conditions, the peptide molecules self-assemble into a dense three-dimensional network of nanofibers, which expose the neuritepromoting laminin epitope.…”

Modular self-assembling biomaterials for directing cellular responses

“…13 An analogous strategy has also been utilized to decorate collagen matrices with peptides able to co-assemble non-covalently into the collagen triple helix.15 Other recent advances in modular self-assemblies have sought not to decorate a base scaffold but to construct the entire material from self-assembling small molecular weight components. For example, Stupp and coworkers recently extended their previous work with peptide-amphiphile biomaterials [16][17][18] by investigating the assembly and bioactivity of new peptide-amphiphiles capable of presenting additional ligands such as biotin, 9,19 RGD, 20,21 and others. 22 In these systems, the ligands are effectively displayed and bioactive, enabling future work where complex combinations of them are tuned.…”

“…Encouraging successes have already been reported using ligand-presenting self-assembling biomaterials to influence a variety of cell behaviors. Representative examples include the differentiation of neural progenitor cells, 16 the adhesion and spreading of fibroblasts, 21 the proliferation and protein expression of endothelial cells, 26,28 the proliferation, differentiation, and migration of osteoblasts, 24 and the intracellular uptake of the material itself. 29 However, the modularity of these materials has not yet been fully exploited, as many simultaneously co-assembled factors have yet to be systematically tuned and optimized.…”