Abstract
Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells’ growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, “IKVAV”, and fibronectin-derived well known adhesive sequence, “RGD”, into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes.
Highlights
Skeletal muscle is a collection of muscle fibers, which function together as a unit to generate contractile longitudinal forces for physical movement
Maturation index, which denotes the prevalence of myotubes with 5 or more nuclei compared to total myotube numbers, was measured. 30% of all myotubes were found to be mature in each group (Fig. 7E). These results demonstrate that IKVAV- and RGD-integrated peptide nanofibers that physically and biochemically mimic the Extracellular matrix (ECM) environment are favorable surfaces for growth and differentiation of C2C12 skeletal myoblast cells
The bioactive peptide nanofiber based system presented in this study constitutes a strong candidacy towards providing myogenic signals to augment muscle regeneration, and preventing infiltration of connective tissue
Summary
Skeletal muscle is a collection of muscle fibers, which function together as a unit to generate contractile longitudinal forces for physical movement. Peptide amphiphiles enable incorporation of various functional biological signals into their primary sequence and give rise to formation of higher order nanostructures that display complex architecture and biochemical characteristics of native tissue microenvironment under physiological conditions[24,26,27] These properties make these molecules ideal candidates to be used as bioactive scaffolds for regenerative medicine and tissue engineering applications. Peptide sequences derived from the active site of the laminin and fibronectin proteins, which have important roles in muscle regeneration and development, were incorporated into peptide amphiphile nanofibers, so that basal lamina composition of skeletal muscle was mimicked. We evaluated the differentiation inducing potential of peptide amphiphiles in skeletal muscle regeneration
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