Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers

Abstract

Investigation of model biomembranes and their interactions with natural or synthetic macromolecules are of great interest to design membrane systems with specific properties such as drug-delivery. Here we study the behavior of amphiphilic β-turn mimetic polymer conjugates at the air-water interface and their interactions with lipid model membranes. For this endeavor we synthesized two different types of conjugates containing either hydrophobic polyisobutylene (PIB, M n = 5000 g·mol −1 ) or helical poly(n-hexyl isocyanate) (PHIC, M n = 4000 g·mol −1 ), both polymers being immiscible, whereas polyisobutylene as a hydrophobic polymer can incorporate into lipid membranes. The conjugates were investigated using Langmuir-film techniques coupled with epifluorescence microscopy and AFM (Atomic Force Microscopy), in addition to their phase behavior in mixed lipid/polymer membranes composed of DPPC (dipalmitoyl-sn-glycero-3-phosphocholine). It was found that the DPPC monolayers are strongly disturbed by the presence of the polymer conjugates and that domain formation of the polymer conjugates occurs at high surface pressures (π > 30 mN·m −1 ).

Secondary Structures in Synthetic Poly(Amino Acids): Homo‐ and Copolymers of Poly(Aib), Poly(Glu), and Poly(Asp)

“…Both, helical turns, substitution patterns and the final conformation can be most delicately tuned by choice of the monomers or their embedded sequence as proven by us and others in the past (see own publications form our group in the context of the CRC 102). [48,49,[56][57][58]66,67,143]…”

“…The so designed synthetic hybrid-molecules represent simplified model systems for the interplay of inter-and intramolecular assembly of (partially un-) folded systems, able to form complex hierarchical assemblies in solution (amyloids, elastins), or materials in the solid, semicrystalline state (such as, e.g., spider-silk [46] or pyro-protein-fibers [47] ). These hybrid molecules contain repetitive units of amino acids (oligo( Bn Asp, Bn Glu, [48,49] or Lysine [50,51] )) as middle segments, purely geometrical constraints [52][53][54][55] including artificial 𝛽-turns, [56][57][58] photoswitchable units [59][60][61] or amyloidogenic peptide-sequences. [62][63][64] They are interrupted by "synthetic" intermissions, basically representing -((CH 2 ) n -units of a precise chain length (n = 16-20).…”

“…The chain length (and thus the number of repetitive units along the chain) could be precisely adjusted by preparative size-exclusion chromatography (SEC) after ADMET, obtaining fractions with narrowly distributed chain lengths. [48,50] The folding/restraining elements could be freely chosen: I,II) purely geometrical constraints based on Hbonding systems; [52][53][54][55] III) azo-switches reminiscent of artificial 𝛽-turn mimetics; [59][60][61] IV-XI) homo poly(amino acids), primarily based on oligo( Bn Asp/ Bn Glu [48,49] ) and poly(Aib)-peptides; [66,67] and (XI) artificial 𝛽-turn mimetics [56,57] and polyisocyanatehelices. [58] Subsequently, these polymers were studied in view of fibrillation, aggregation, and chirality transfer.…”