Synthesis and Characterization of Well-Defined PEGylated Polypeptoids as Protein-Resistant Polymers

Well-defined polypeptoids bearing oligomeric ethylene glycol side chains (PNMe­(OEt)_<i>n</i>G, <i>n</i> = 1–3) with a controlled molecular weight (3.26–28.6 kg/mol) and narrow molecular weight distribution (polydispersity index, PDI = 1.03–1.10) have been synthesized by ring-opening polymerization of the corresponding <i>N</i>-carboxyanhydrides having oligomeric ethylene glycol side chains (Me­(OEt)_<i>n</i>-NCA, <i>n</i> = 1–3) using primary amine initiators. Kinetic studies of polymerization revealed a first-order dependence on the monomer concentration, consistent with living polymerization. The obtained PEGylated polypeptoids are highly hydrophilic with good water solubility (>200 mg/mL) and are amorphous, with a glass transition temperature in the −41.1 to +46.4 °C range that increases with increasing molecular weight and decreasing side chain length. DLS and SANS analyses revealed no appreciable adsorption of lysozyme to PNMeOEtG. PNMeOEtG having different molecular weights exhibited minimal cytotoxicity toward HEp2 cells. These combined results suggest the potential use of PEGylated polypeptoids as protein-resistant materials in biomedical and biotechnological fields

Solution Self-Assemblies of Sequence-Defined Ionic Peptoid Block Copolymers

A series of amphiphilic ionic peptoid block copolymers where the total number (1 or 3) and position of ionic monomers along the polymer chain are precisely controlled have been synthesized by the submonomer method. Upon dissolution in water at pH = 9, the amphiphilic peptoids self-assemble into small spherical micelles having hydrodynamic radius in ∼5–10 nm range and critical micellar concentration (CMC) in the 0.034–0.094 mg/mL range. Small-angle neutron scattering (SANS) analysis of the micellar solutions revealed unprecedented dependence of the micellar structure on the number and position of ionic monomers along the chain. It was found that the micellar aggregation number (<i>N</i>_agg) and the micellar radius (<i>R</i>_m) both increase as the ionic monomer is positioned progressively away from the junction of the hydrophilic and hydrophobic segments along the polymer chain. By defining an ionic monomer position number (<i>n</i>) as the number of monomers between the junction and the ionic monomer, <i>N</i>_agg exhibited a power law dependence on <i>n</i> with an exponent of ∼1/3 and ∼3/10 for the respective singly and triply charged series. By contrast, <i>R</i>_m exhibited a weaker dependence on the ionic monomer position by a power law relationship with an exponent of ∼1/10 and ∼1/20 for the respective singly and triply charged series. Furthermore, <i>R</i>_m was found to scale with <i>N</i>_agg in a power-law relationship with an exponent of 0.32 for the singly charged series, consistent with a weakly charged ionic star-like polymer model in the unscreened regime. This study demonstrated a unique method to precisely tailor the structure of small spherical micelles based on ionic block copolymers by controlling the sequence and position of the ionic monomer

Nanoscale Lipid/Polymer Hybrid Vesicles: Effects of Triblock Copolymer Composition and Hydrophilic Weight Fraction

Hybrid vesicles resulting from combined self-assembly of polymers and lipids have gained interest in recent years as drug delivery systems, biosensors, and model systems for structural scaffolds as artificial organelles. So far, in the literature, more attention has been given to study how the discrepancy of chemical compositions and hydrophobic segment sizes between polymers and lipids affect the vesicle’s nature. In this study, we focused on how the hydrophilic blocks impact the vesicle’s morphology. Therefore, we developed hybrid lipid/polymer vesicle systems with lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and amphiphilic triblock copolymers composed of poly(ethylene glycol)–poly(dimethylsiloxane)–poly(ethylene glycol) (PEG–PDMS–PEG). Three types of hybrid vesicle systems were investigated in a systematic manner by changing the hydrophilic block length and the polymer–lipid composition. From the data obtained from cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering, we observed that the hydrophilic mass fraction of an amphiphilic polymer can affect the membrane thickness, size polydispersity, and lamellarity of polymer/lipid hybrid vesicles

Dynamics of Phospholipid Membranes beyond Thermal Undulations

We investigated the molecular dynamics of unilamellar liposomes by neutron spin echo spectroscopy. We report the first experimental evidence of a short-range motion at the length scale of the size of the headgroup of a lipid. The associated mean squared displacement shows a <i>t</i>^0.26 dependence in the pico- to nanosecond region that indicates another process beyond the predictions of the Zilman–Granek (ZG) model (<i>t</i>^0.66) and translational diffusion (<i>t</i>¹). A comparison with theory shows that the observed low exponent is associated with a non-Gaussian transient trapping of lipid molecules in a local area and supports the continuous time random walk model. The analysis of the mean squared displacement leads to the important conclusion that the friction at the interface between water and liposomes plays a minor role. Center of mass diffusion of liposomes and transient trapping of lipids define the range in which the ZG model can be applied to analyze membrane fluctuations

Monitoring the Internal Structure of Poly(<i>N</i>‑vinylcaprolactam) Microgels with Variable Cross-Link Concentration

The combination of a set of complementary techniques allows us to construct an unprecedented and comprehensive picture of the internal structure, temperature dependent swelling behavior, and the dependence of these properties on the cross-linker concentration of microgel particles based on <i>N</i>-vinylcaprolactam (VCL). The microgels were synthesized by precipitation polymerization using different amounts of cross-linking agent. Characterization was performed by small-angle neutron scattering (SANS) using two complementary neutron instruments to cover a uniquely broad Q-range with one probe. Additionally we used dynamic light scattering (DLS), atomic force microscopy (AFM), and differential scanning calorimetry (DSC). Previously obtained nuclear magnetic resonance spectroscopy (NMR) results on the same PVCL particles are utilized to round the picture off. Our study shows that both the particle radius and the cross-link density and therefore also the stiffness of the microgels rises with increasing cross-linker content. Hence, more cross-linker reduces the swelling capability distinctly. These findings are supported by SANS and AFM measurements. Independent DLS experiments also found the increase in particle size but suggest an unchanged cross-link density. The reason for the apparent contradiction is the indirect extraction of the parameters via a model in the evaluation of DLS measurements. The more direct approach in AFM by evaluating the cross section profiles of observed microgel particles gives evidence of significantly softer and more deformable particles at lower cross-linker concentrations and therefore verifies the change in cross-link density. DSC data indicate a minor but unexpected shift of the volume phase transition temperature (VPTT) to higher temperatures and exposes a more heterogeneous internal structure of the microgels with increasing cross-link density. Moreover, a change in the total energy transfer during the VPT gives evidence that the strength of hydrogen bonds is significantly affected by the cross-link density. A strong and reproducible deviation of the material density of the cross-linked microgel polymer chains toward a higher value compared to the respective linear chains has yet to be explained