Molecular mechanisms of electric field-induced modulation of responsive surface structures and protein behavior

Abstract

Protein behavior on electro-responsive surfaces is critical for various biotechnological applications. Molecular simulations were used to investigate the effects of external electric fields (EFs) on the structure and wettability of mixed SAMs comprising long carboxyl/carboxylate-terminated chains and short hydroxyl‑terminated chains with varying surface charge densities (SCDs), as well as their resulting influence on protein behaviors. Analysis reveals that without external EFs, increased SCD leads to higher degrees of disorder in carboxyl/carboxylate-terminated chains. Under a positive EF, as the SCD rises, more carboxylate-terminated chains align straight, exposing charged groups on the outermost layer of the SAMs, thereby increasing the surface hydrophilicity. Under a negative EF, as SCD increases, more carboxylate-terminated chains bend, exposing the alkyl parts and burying the charged groups within the SAMs, thereby enhancing surface hydrophobicity. When fully deprotonated, the SAM generates alternating hydrophobic and hydrophilic regions. Both positive and negative EFs weakened the protein-surface interactions. The former is attributed to the formation of the more tightly bound water layer and the shielding effect of counterions; whereas the latter is due to the reduced electrostatic interactions and competition from counterions. Lysozyme primarily adsorbs onto the SAMs through its right side. However, under conditions of high SCD and a positive EF, lysozyme adsorbs via its bottom site, where its active site is easily accessible. Lysozyme conformation changes irregularly with SCD under an electric field on SAMs, depending on the coupling interactions between protein and surface. These findings provide valuable insights into the design of electro-responsive surfaces for biotechnological applications.