Magnetic Field-Induced Alignment of Nanofibrous Supramolecular Membranes: A Molecular Design Approach to Create Tissue-like Biomaterials.

A molecular design approach to fabricate nanofibrous membranes by self-assembly of aromatic cationic peptides with hyaluronic acid (HA) and nanofiber alignment under a magnetic field is reported. Peptides are designed to contain a block composed of four phenylalanine residues at the C-terminus, to drive their self-assembly by hydrophobic association and aromatic stacking, and have a positively charged domain of lysine residues for electrostatic interaction with HA. These two blocks are connected by a linker with a variable number of amino acids and the ability to adopt distinct conformations. Zeta potential measurements and circular dichroism confirm their positive charge and variable conformation (random coil, ß-sheet, or α-helix), which depend on the pH and sequence. Their self-assembly, examined by fluorescence spectroscopy, small-angle X-ray scattering, and transmission electron microscopy, show the formation of fiberlike nanostructures in the micromolar range. When the peptides are combined with HA, hydrogels or flat membranes are formed. The molecular structure tunes the mechanical behavior of the membranes and the nanofibers align in the direction of magnetic field due to the high diamagnetic anisotropy of phenylalanine residues. Mesenchymal stem cells cultured on magnetically aligned membranes elongate in direction of the nanofibers supporting their application for soft tissue engineering.

Supramolecular Presentation of Hyaluronan onto Model Surfaces for Studying the Behavior of Cancer Stem Cells.

The supramolecular presentation of extracellular matrix components on surfaces provides a platform for the investigation and control of cell behavior. Hyaluronan (HA) is one of the main components of the extracellular environment and has been shown to play an important role in different cancers and their progression. However, current methods of HA immobilization often require its chemical modification. Herein, a peptide-based self-assembled monolayer (SAM) is used as an anchor to immobilize unmodified HA on a bare gold surface, as demonstrated by the quartz crystal microbalance with dissipation monitoring. Peptide-HA surfaces show increased roughness and greater hydrophobicity when compared to poly-D-lysine/HA surfaces, as measured by atomic force microscopy and water contact angle, respectively. Additionally, the peptide SAM can be micro-contact printed and used to restrict the presentation of HA to specific regions, thereby creating HA patterned surfaces to examine cell behavior. When used for cell culture, these surfaces result in altered adhesion and migration of LUC4 head and neck squamous cell carcinoma cells. These biomimetic surfaces can provide insights into the role of HA in cancer and other diseases and be used as a platform for the development of cell sorting devices.