Publications

Supramolecular self-assembled systems have emerged as versatile platforms for engineering biomimetic environments that precisely regulate cellular behavior. These materials have tunable properties such as stiffness, hydrophobicity, and molecular composition, allowing for customization of their structure and function. Despite significant advances, the specific role of electrostatic properties in modulating cellular responses within supramolecular assemblies remains poorly understood. Here, a peptide library with diverse electrostatic profiles is designed to systematically investigate their influence on the bioactivity of supramolecular assemblies for neural regeneration. Combining computational and experimental methods, the self-assembly conditions of these peptides are optimized to create stable, biologically relevant architectures. Using human neural progenitor cell (hNPC) cultures, it is demonstrated that negatively charged environments enhance cell survival and promote neuronal differentiation. Specifically, high negative charges activate critical signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade and cell adhesion mechanisms, leading to neuronal lineage commitment. This study establishes a novel framework for the design of supramolecular systems, offering an unprecedented ability to analyze specific parameters in cell behavior. By achieving control beyond conventional biomaterials, this work provides valuable insights into the complex interplay of biophysical and biochemical cues in the native neural microenvironment, with implications for regenerative medicine and biomaterial design.

JTD Keywords: Charge screening, Death, Design, Extracellular-matrix, Force-field, Human neural progenitor cells, Membrane, Molecular dynamics, Nervous-system, Proteomics, Scaffolds, Self-assemblies, Supramolecular structures

Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphe-nylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N-and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylme-thyloxycarbonyl and benzyl ester end-capping groups at the N-and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in beta-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm beta-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the mediu m on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addi-tion, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of pi-pi stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which de-termines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.

JTD Keywords: aromatic interactions, beta-sheet, hierarchical structures, phenylalanine homopeptides, supramolecular structures, Amino-acids, Aromatic interactions, Beta-sheet, Dipeptides, Diphenylalanine, Fmoc, Hierarchical struc tures, Hierarchical structures, Hydrogels, Peptides, Phenylalanine, Phenylalanine homopeptides, Solvent, Solvents, Spectroscopy, Supramolecular structures, Triphenylalanine