Aggregation dynamics of methacrylate binary and ternary biomimetic polymers in solution

Abstract

Using detailed atomistic simulations,we explore the conformational landscape of aggregates formed by biomimetic antimicrobial(AM) binary methacrylate copolymers,with hydrophobic and charged functional groups and the role of inclusion of polar functional groups on such aggregate morphologies.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 suggest that block binary copolymers form large spherical aggregates with effective shielding of hydrophobic groups by charged groups.In contrast, random binary copolymers tend to form more bundle-like structures with exposed hydrophobic groups.The strong aggregation of binary polymers is driven primarily by attractive interactions between hydrophobic groups.However,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 case of random ternary polymers.Interaction energy calculations strongly suggest that the role of inclusion of polar groups is two-fold: (1)to reduce possible strong local concentration of hydrophobic groups and smear the 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 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 behavior into bacterial and mammalian membranes.