Self-Assembly of a Conjugate of Lipoic Acid With a Collagen-Stimulating Pentapeptide Showing Cytocompatibility and Wound Healing Properties, and Chemical and Photolytic Disassembly

Abstract

Lipoic acid is a biocompatible compound with antioxidant activity that is of considerable interest in cosmetic formulations, and the disulfide group in the N-terminal ring confers redox activity. Here, we study the self-assembly and aspects of the bioactivity of a lipopeptide (peptide amphiphile) comprising the KTTKS collagen-stimulating pentapeptide sequence conjugated to an N-terminal lipoic acid chain, lipoyl-KTTKS. Using SAXS, SANS and cryo-TEM, lipoyl-KTTKS is found to form a population of curly fibrils (wormlike micelles) above a critical aggregation concentration. Upon chemical reduction, the fibrils (and β-sheet structure) are disrupted because of the breaking of the disulfide bond, which produces dihydrolipoic acid. Lipoyl-KTTKS also undergoes photo-degradation in the presence of UV radiation. Through cell assays using fibroblasts, we found that lipoyl-KTTKS has excellent cytocompatibility across a wide concentration range, stimulates collagen production, and enhances the rate of cell coverage in a simple in vitro scratch assay of ‘wound healing’. Lipoyl-KTTKS thus has several notable properties that may be useful for the development of cosmetics, cell scaffolds or tissue engineering materials.