The MARTINI coarse-grain (CG) force field is extended for a class of triblock block copolymers known as Pluronics. Existing MARTINI bead types are used to model the non-bonded part of the potential while single chain properties for both homopolymers, poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), are used to develop the bonded interactions. The new set of force field parameters reproduces structural and dynamical properties of high molecular weight homo- and copolymers. The CG model is moderately transferable in solvents of different polarity and concentration; however, the PEO homopolymer model presents a reduced thermodynamic transferability especially in water probably due to the lack of hydrogen bonds with the solvent. Our simulations of a monolayer of Pluronic L44 show polymer-brush-like characteristics for the PEO segments which protrude into the aqueous phase. Other membrane properties not easily accessible using experimental techniques such as its membrane thickness are also calculated.

Poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block co-polymers (PEO-PPO-PEO, sold as Pluronics, Poloxamers, Tetronics) are a widely used class of amphiphilic materials for different biological applications. In fact for certain members of the Pluronics series, the interactions of block segments with living cells alter the lipid membrane properties and facilitate the permeation of drugs. A fuller understanding of the molecular mechanisms underpinning these interactions is essential for ensuring their safety and efficacy in biomedical applications and to inform the design of new amphiphilic copolymers for potential use in a clinical setting. In this paper, by means of atomistic molecular dynamics simulations and membrane lysis assays, we investigate the relationship between the molecular conformations of a subset of the Pluronic copolymers (L31, L61, L62 and L64) and their haemolytic activity. Our computational studies suggest that the hydrophilic blocks in these copolymers interact with the polar head groups of lipid molecules, resulting in a predicted modification of the structure of the membranes. Parallel membrane lysis assays in human erythrocytes indicate differences in the rates of haemolysis, as a result of incubation with these polymers, that correlate well with the predicted interactions from the atomistic simulations. The computational data thus provide a putative mechanism to rationalize the available experimental data on membrane lysis by these copolymers and quantitatively agree with haemoglobin release endpoints measured when copolymers with the same molecular weight and structure as of those modelled are incubated with erythrocytes. The data further suggest some new structure-function relationships at the nanoscale that are likely to be of importance in determining the biological activity of these otherwise inert copolymers.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

The data suggest a link between the affinity of certain Pluronics for biological membranes and their cellular adverse effects. This first cell-based investigation of the interactions of Pluronics with biological membranes is an important step towards unravelling the complex mechanisms which govern the biological effects of widely used amphiphilic materials.

Molecules that are the size of small proteins are difficult to make. The most frequently examined route is via self-assembly, and one particular approach involves molecular nanocapsules, where ligands are designed that will enforce the formation of specific polyhedra of metals within the core of the structure. Here we show that this approach can be combined with mechanically interlocking molecules to produce nanocapsules that are decorated on their exterior. This could be a general route to very large molecules, and is exemplified here by the synthesis and structural characterization of a [13]rotaxane, containing 150 metal centres. Small angle X-ray scattering combined with atomistic molecular dynamics simulations demonstrate the compound is intact in solution.