Aggregation of methacrylate-based ternary biomimetic antimicrobial polymers in solution

Abstract

Using detailed atomistic simulations, we explore the morphological characteristics of aggregates formed in solution phase by ternary biomimetic antimicrobial (AM) methacrylate polymers, composed of hydrophobic, charged cationic and polar functional groups and compare it with aggregate morphologies of binary methacrylate polymers, composed only of hydrophobic and charged cationic functional groups. The effect of sequence of the constituent functional groups on aggregate conformation is also studied by considering random and block sequences along the polymer backbone. Our results show that while binary polymers tend to form robust aggregates, replacing some of the hydrophobic groups with overall charge neutral polar groups weakens the aggregate considerably, leading to increased conformational fluctuations and formation of loose-packed, open aggregates, particularly in the case of random ternary polymers. Interaction energy calculations clearly suggest that the role of inclusion of polar groups in ternary polymers is two-fold: (1) to reduce possible strong local concentration of hydrophobic groups and ‘smear’ the overall hydrophobicity along the polymer backbone to increase the solubility of the polymers (2) to compensate the loss of attractive hydrophobic interactions by forming attractive electrostatic interactions with the charged groups and contribute to aggregation formation, albeit weak. Given that most of the naturally occurring AM peptides have contributions from all the three functional groups, this study elucidates the functionally tuneable role of inclusion of polar groups in the way AM agents interact with each other in solution phase, which can eventually dictate their partitioning behaviour into bacterial and mammalian membranes.