Supramolecular Peptide Nanofiber Morphology Affects Mechanotransduction of Stem Cells

Abstract

Chirality and morphology are essential factors for protein function and interactions with other biomacromolecules. Extracellular matrix (ECM) proteins are also similar to other proteins in this sense; however, the complexity of the natural ECM makes it difficult to study these factors at the cellular level. The synthetic peptide nanomaterials harbor great promise in mimicking specific ECM molecules as model systems. In this work, we demonstrate that mechanosensory responses of stem cells are directly regulated by the chirality and morphology of ECM-mimetic peptide nanofibers with strictly controlled characteristics. Structural signals presented on l-amino acid containing cylindrical nanofibers (l-VV) favored the formation of integrin β1-based focal adhesion complexes, which increased the osteogenic potential of stem cells through the activation of nuclear YAP. On the other hand, twisted ribbon-like nanofibers (l-FF and d-FF) guided the cells into round shapes and decreased the formation of focal adhesion complexes, which resulted in the confinement of YAP proteins in the cytosol and a corresponding decrease in osteogenic potential. Interestingly, the d-form of twisted-ribbon like nanofibers (d-FF) increased the chondrogenic potential of stem cells more than their l-form (l-FF). Our results provide new insights into the importance and relevance of morphology and chirality of nanomaterials in their interactions with cells and reveal that precise control over the chemical and physical properties of nanostructures can affect stem cell fate even without the incorporation of specific epitopes.

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

“…Hence, it can be concluded that osteogenesis will be enhanced on any substrate in which cells display stronger adhesion and greater spreading via increased integrin clustering and FA formation. For example, Arslan et al (2017) demonstrated conclusively that nanofiber morphology exerts a profound effect on cellular YAP activation and osteogenesis via modulation of integrin clustering. In particular, cylindrical peptide nanofibers facilitated the formation of integrin β1-based FA complexes, which in turn enhanced the osteogenic potential of stem cells through increased YAP activation, whereas twisted ribbon-like nanofibers had the opposite effect (Arslan et al, 2017).…”

“…For example, Arslan et al (2017) demonstrated conclusively that nanofiber morphology exerts a profound effect on cellular YAP activation and osteogenesis via modulation of integrin clustering. In particular, cylindrical peptide nanofibers facilitated the formation of integrin β1-based FA complexes, which in turn enhanced the osteogenic potential of stem cells through increased YAP activation, whereas twisted ribbon-like nanofibers had the opposite effect (Arslan et al, 2017). Likewise, in an interesting study by Wang et al (2016), micropatterned substrates enabled precise control of the spreading and adhesion area of human MSCs, and it was found that a larger cell adhesion area promoted both YAP/TAZ activation and osteogenesis, while a smaller cell adhesion area reduced TAP/TAZ activity and promoted adipogenic differentiation.…”

“…On fibrous substrates, the chirality and morphology of the nanofibers have a profound effect on chondrogenic differentiation. Arslan et al (2017) found that the d-form of twisted-ribbon like nanofibers (d-FF) enhanced the chondrogenic potential of stem cells more than their l-form (l-FF) by guiding the cells into round shapes and decreasing the formation of FA complexes (Arslan et al, 2017). Besides the mechanical properties of the substrata, chondrocytes are also sensitive to mechanical forces.…”

“…Thirdly, we may exploit our new knowledge of YAP/TAZ signaling mechanisms to optimize the therapeutic properties of newly developed biomaterials. By performing YAP/TAZ assays on relevant cell lineages cultured on newly developed biomaterials in vitro , we may be able to fine-tune various biomechanical properties such as stiffness ( Dupont et al, 2011 ; Nardone et al, 2017 ; Pardo-Pastor et al, 2018 ) and topography ( Yang W. et al, 2016 ; Zhang Y. et al, 2016 ; Arslan et al, 2017 ; Hwang et al, 2017 ; Qian et al, 2017 ), enabling us to optimize the healing and regeneration processes at specific tissue/organ sites with implanted biomaterials.…”

Highly Elastic and Water Stable Zein Microfibers as a Potential Drug Delivery System for Wound Healing

“…This is the result of the fast evaporation of ethanol from the surface, leading to the formation of a skin around the fibers, which collapses when the solvent within the fibers evaporates completely [15,27]. However, it has been shown that cells prefer tubular-shaped fibers for proliferation [28]. Researchers have therefore attempted to obtain tubular-shaped fibers by dissolving zein in organic solvents such as glacial acetic acid [29], or through the addition of polyethylene oxide (PEO) directly to zein in aqueous ethanol solution, followed by aging the mixture for several days to enhance hydration of its interior [30].…”