Two-Dimensional Peptide Assembly via Arene–Perfluoroarene Interactions for Proliferation and Differentiation of Myoblasts

Abstract

Supramolecular assembly based on aromatic interactions can provide well-defined nanostructures with an understanding of intermolecular interactions at the molecular level. The peptide assembly via a supramolecular approach can overcome the inherent limitations of bioactive peptides, such as proteolytic degradations and rapid internalizations into the cytosol. Although extensive research has been carried out on supramolecular peptide materials with a two-dimensional (2D) structure, more needs to be reported on biological activity studies using well-defined 2D peptide materials. Physical and chemical properties of the 2D peptide assembly attributed to their large surface area and flexibility can show low cytotoxicity, enhanced molecular loading, and higher bioconjugation efficiency in biological applications. Here, we report supramolecular 2D materials based on the pyrene-grafted amphiphilic peptide, which contains a peptide sequence (Asp-Gly-Glu-Ala; DGEA) that is reported to bind to the integrin α2β1 receptor in 2D cell membranes. The addition of octafluoronaphthalene (OFN) to the pyrene-grafted peptide could induce a well-ordered 2D assembly by face-centered arene–perfluoroarene stacking. The DGEA-peptide 2D assembly with a flat structure, structural stability against enzymatic degradations, and a larger size can enhance the proliferation and differentiation of muscle cells via continuous interactions with cell membrane receptors integrin α2β1 showing a low intracellular uptake (15%) compared to that (62%) of the vesicular peptide assembly. These supramolecular approaches via the arene–perfluoroarene interaction provide a strategy to fabricate well-defined 2D peptide materials with an understanding of assembly at the molecular level for the next-generation peptide materials.

Peptide Assembly of Different Dimensions and Their Effect on Myoblast Proliferation

“…These results demonstrated the potential of 2-D peptide assembly for biological applications due to their unique properties and versatility, such as the target molecule detection ability, molecular loading ability, and bioconjugation efficiency of the materials . However, although previous studies have compared the biological activity of 2-D and 3-D peptide assemblies well, a comparative study between 1-D and 2-D peptide assemblies has not been performed as part of a study to find the optimal dimension in peptide assemblies. Furthermore, research on RGD-based 2-D supramolecular structures has been rarely studied.…”

“…30,31 Recently, our group reported different biological functions between small vesicular assembly (3-D) and large 2-D assembly, which contains a peptide sequence (Asp-Gly-Glu-Ala; DGEA) derived from collagen type I protein. 31 The 2-D peptide assembly enhanced the proliferation and differentiation of muscle cells compared with 3-D vesicular assembly due to a flat structure, structural stability against enzymatic degradations, and a larger size. These results demonstrated the potential of 2-D peptide assembly for biological applications due to their unique properties and versatility, such as the target molecule detection ability, molecular loading ability, and bioconjugation efficiency of the materials.…”

“…The morphology of peptide assemblies can influence their interactions with biological systems, such as cells, enzymes, and tissues, and ultimately modulate their bioactivity . For example, the peptide assemblies with different morphologies may provide different degrees of protection or stability of the conjugated bioactive molecules. , Recently, our group reported different biological functions between small vesicular assembly (3-D) and large 2-D assembly, which contains a peptide sequence (Asp-Gly-Glu-Ala; DGEA) derived from collagen type I protein . The 2-D peptide assembly enhanced the proliferation and differentiation of muscle cells compared with 3-D vesicular assembly due to a flat structure, structural stability against enzymatic degradations, and a larger size.…”

Self-assembly of cyclic peptide monolayers by hydrophobic supramolecular hinges

“…8 Yet, the high surface area of 2D assemblies is highly coveted by material scientists and supramolecular chemists alike, finding applications in catalysis, 9,10 molecular sieving, 11 responsive surfaces 12,13 and biosensing, 14,15 amongst others. 16,17…”

DNA Origami Tessellations

“…In particular, the tessellation of nanoscale building blocks, including colloidal nanoparticles, , organic compounds, − and biomolecules − via bottom-up self-assembly, provides a versatile means of engineering two-dimensional materials whose properties can be tailored by altering the long-range order or the local arrangement of constituent units, which has been the common focus of nanomaterials, supramolecular chemistry, and molecular sciences. Exotic properties can emerge from the ordered arrangements of functional modules that interact with and modulate electromagnetic waves, , electric or magnetic fields, , and cells, , holding promise for applications in photonic crystals, plasmonic metamaterials, electronics, and bioactive materials. However, the lack of inherent modularity and customizable specificity in the majority of nanoobjects has limited the diversity and efficiency of tessellation dictated solely by their intrinsic self-organizing properties, necessitating the development of a versatile scaffolding material that simultaneously endows the target nanoobject with long-range order and local precision.…”