The Importance of Molecular Size, Concentration, and Thermal Conditions in Enhancing Lignin Derivatives' Interactions with Skin-like Membranes: Implications for Cosmetic and Therapeutic Applications.

Lignin is one of the most abundant natural biopolymers and plays a crucial role in the development of safe and sustainable alternatives for healthcare products. In this study, we employed molecular dynamics simulations and free energy calculations to investigate lignin derivatives' interactions with skin-like membranes. Specifically, we designed a small lignin derivative composed of syringyl and guaiacyl subunits. Our results reveal that molecular size, concentration, and thermal conditions critically influence the insertion, interaction dynamics, and localization behavior of lignin derivatives. Notably, variations in these parameters induce distinct behaviors, including rapid membrane insertion, hydrogen bonding, clustering, and surface adhesion. The findings provide insights into the molecular mechanisms governing lignin derivatives' interactions with skin-like membranes, with implications for developing bio-based skincare formulations and transdermal delivery systems. Our results highlight the importance of molecular size and concentration in optimizing lignin-derived compounds for dermatological and therapeutic applications.