We have investigated the dynamics of nonentangled and weakly entangled polyisoprene (PI) melts using neutron spin echo spectroscopy and pulsed field gradient NMR and compared the spectra with those from a highly entangled PI melt. Except for Brownian diffusion, which was observed in the long-time regime using NMR, the spectra from nonentangled and weakly entangled PI chains were identical. Dividing out Brownian diffusion, these reduced spectra also quantitatively agree with those from the highly entangled PI melt. Reevaluating the results for poly(butylene oxide) leads to an identical observation, indicating universality. These experiments provide quantitative proof of key predictions of theory: (i) the correlation hole potential governs both the subdiffusivity of nonentangled systems and the cooperative dynamics within the entanglement volume, and (ii) as the spectra from a weakly entangled PI melt also coincide with those from the shorter and highly entangled PI, the entanglement potential, which creates topological constraints, acts in the same way for weakly and strongly entangled melts.

For almost 30 years, the Zilman-Granek stretched exponential [Zilman & Granek (1996). Phys. Rev. Lett. 77, 4788-4791] has been used to obtain bending rigidities of membranes in lipid and surfactant vesicles from neutron spin echo data. However, with the advent of improved spectrometers that can easily measure Fourier times up to some 100 ns and even 1 µs, more subtle effects become visible in the data, which requires a refined theory. Recently, we published a framework for analysing such neutron spin echo data [Granek et al. (2024). Eur. Phys. J. E 47, 12]. Here, we apply this framework to different model membranes. The purpose of this paper is twofold. We intend to elucidate some often overlooked parameters, such as vesicle diffusion, size, lamellarity and membrane tension, that limit the quantitative interpretation of bending modulus values from NSE data. We also present some future opportunities to better understand the membrane dynamics and major sources of dissipation at the nanoscale uniquely probed with NSE.

Neutron spin echo (NSE) spectroscopy is a powerful technique used to probe the internal dynamics and diffusion processes within matter, allowing researchers to quantify how materials respond to changes in external conditions. To fully understand the bulk properties of a material, it is often crucial to investigate dynamic processes occurring on nanometre length scales and nanosecond timescales. NSE spectroscopy provides an exceptional capability to measure such dynamics across a broad spectrum of condensed matter systems, ranging from proteins and quantum magnets to catalysts. In this Primer, we present an overview of NSE spectroscopy, highlighting the instruments used, methods of data collection and representative applications in both soft-matter and hard-matter sciences. Neutron spin echo spectroscopy investigates internal dynamics and diffusion in materials, using advanced instruments and data collection techniques. In this Primer, Faraone et al. discuss how neutron spin echo spectroscopy can be used in both soft-matter and hard-matter sciences.

Biological lipid membranes can be mimicked by small unilamellar vesicles (SUVs), which e.g. consist of the negatively charged phospholipid 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG). Due to the unsaturated hydrocarbon chains and hence the low main phase transition temperature, a DOPG membrane is always fluid-like in aqueous solution. By addition of cholesterol to the DOPG model membrane, the membrane stiffness is found to increase. These cholesterol-containing DOPG SUVs are characterized in the presence of varying amounts of the saponins aescin and glycyrrhizin at a temperature of 30°C by diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY NMR), small-angle neutron scattering (SANS), small- and wide-angle X-ray scattering (SAXS, WAXS), neutron spin echo spectroscopy (NSE), and cryogenic transmission electron microscopy (cryo-TEM). All methods reveal that cholesterol is incorporated into the long-term stable SUVs. Upon saponin addition up to a molar ratio of 1:1 no significant modifications of the SUV size parameters are detected. However, NSE reveals a slight alteration in the membrane elasticity. In sum, the DOSY NMR and scattering results clearly show the coexistence of DOPG-cholesterol SUVs and saponin unimers or micelles and an interaction from the outside of the DOPG vesicles seems to promote the change in the membrane rigidity.

Neutron spin echo (NSE) spectroscopy provides unique access to microscopic dynamics, but its application is often constrained by low neutron flux, long acquisition times, and significant noise. We present a Bayesian inference approach based on Gaussian process regression (GPR) to reconstruct high-quality spin echo signals from sparse and noisy data by exploiting correlations in reciprocal space. Benchmarks on synthetic datasets and validation with experimental NSE measurements of dendrimers show that GPR suppresses noise, interpolates missing intensity values, and accommodates irregular observations. The method improves accuracy, shortens acquisition times, and enables high-throughput and real-time studies. Beyond NSE, the framework is broadly applicable to other low signal-to-noise ratio scattering techniques, thereby extending the scope of neutron spectroscopy.

Glycolipids are known to stabilize biomembrane multilayers through preferential sugar-sugar interactions that act as weak transient membrane cross-links. Here, we use small-angle and quasi-elastic neutron scattering on oligolamellar phospholipid vesicles containing defined glycolipid fractions in order to elucidate the influence of glycolipids on membrane mechanics and dynamics. Small-angle neutron scattering (SANS) reveals that the oligolamellar vesicles (OLVs) obtained by extrusion are polydisperse with regard to the number of lamellae, n, which renders the interpretation of the quasi-elastic neutron spin echo (NSE) data nontrivial. To overcome this problem, we propose a method to model the NSE data in a rigorous fashion based on the obtained histograms of n and on their q-dependent intensity-weighted contribution. This procedure yields meaningful values for the bending rigidity of individual lipid membranes and insights into the mechanical coupling between adjacent membrane lamellae including the effect of the glycolipids.

Due to their specificity and versatility, monoclonal antibodies (mAbs) are the most popular class of biopharmaceuticals typically administered via intravenous injection. One of the current pharmaceutical challenges concerns mAb formulations for subcutaneous (SC) injection, which is gaining importance as an alternative administration route offering convenience to patients by allowing self-administration compared to other parenteral delivery methods. With volumes lower than 1-2 mL being better tolerated in the subcutaneous space, highly concentrated mAb formulations are needed to achieve significant therapeutic effects, potentially increasing the solution viscosity and altering drug injectability. The main challenge is to maintain the solution viscosity below the SC injectability threshold (15-20 mPa·s) while preserving solution stability. Since the understanding of macroscopic viscosity requires in-depth knowledge on protein multiscale diffusion, mutual interactions, and aggregation, we employ two complementary neutron scattering techniques to investigate 9 different mAbs of IgG1/IgG4 subtypes in aqueous solution as a function of protein concentration and temperature. The synergy between neutron spin-echo (NSE), a spectroscopy technique providing dynamic information, and small-angle neutron scattering (SANS), a time-averaged static technique, enables us to probe the short-time collective diffusion of different mAbs, explore their self-association into small transient clusters, their intermolecular interactions, and ultimately access their internal dynamics. This study builds on previous neutron backscattering (NBS) findings, bridging a critical gap between the time scales probed by NBS and viscometry. It also confirms that the formation of short-lived clusters comprising more than two monomers is a key factor driving high solution viscosity, phase separation, and opalescence.

We use SANS and TEM to elucidate the shape of the micelles that a spiropyran (SP) surfactant forms. Being both pH- and photo-switchable to a less surface active merocyanine (MC) form, we find that their micelles are of cylindrical shape in any case, which leads us to conclude that the surfactant always switches to its SP form when micellising.

In spite of the numerous studies dealing with the interaction between lipid membranes and surfactants at subsolubilizing membrane concentrations, quantifying detailed bilayer structure, as for instance pore formation, on phospholipid bilayers upon addition of single chain lipids continues to be a challenge. Herein, we analyze the effects of lysophosphatidylcholine (18 : 1 LPC or lysolipid) on soybean phosphatidylcholine (SPC) extruded liposomes, where vesicles containing additional LPC exhibit approximately a 10% reduction in size as indicated by dynamic light scattering experiments. Most importantly, we benefit from the non-perturbing nature of small-angle neutron scattering (SANS) measurements to determine the degree of water incorporation presumably through the surfactant stabilized pores along the fluid bilayers. Model-free analysis of SANS curves reveals that the membrane part of the pure SPC vesicles contain 3.3% v of water. As the lysolipid is added to the dispersion, the volume fraction of water counted into the lipid membrane () increases to 15-20%. Finally, assuming to be equivalent to the volume fraction of pores within the bilayers we estimate the pore size and density.

A fundamental feature of the antibody structure is the flexible linker between the 3 fragments that allows great flexibility and simultaneous binding to epitopes of antigens and receptors. Combining dynamic light scattering, neutron spin-echo spectroscopy and PFG-NMR we determine characteristic internal fragment dynamics on top of translational and rotational diffusion under crowding conditions. Short-time and long-time translational diffusion show an effective hard sphere like behavior within a colloidal picture. Internal fragment motions are characterized as "attack" and "search" motions complemented by rotational fragment motions. We find that the "attack" motions exposing the binding domain are highly preserved from low to physiologically relevant concentrations and higher, while "search" motions and overall rotational diffusion are suppressed under crowding conditions. Hydrodynamic interactions change the friction between fragments determining relaxation times while interparticle interactions influence the strength of the entropic spring between fragments. The strategic redesign of the linker region to facilitate "attack" motions and fragment rotation has the potential to enhance the therapeutic efficacy of mAbs.

Mixtures of the zwitterionic surfactant TDMAO and the anionic surfactant LiPFOS spontaneously self-assemble into well defined vesicles. The size of these vesicles is determined by the ratio of bending rigidity and line tension. By partially charging TDMAO, and thereby moving more to a catanionic system, the size of these vesicles can be controlled. Using stopped flow small angle neutron scattering we monitor the kinetics of vesicle formation and obtain their final size. Neutron spin echo spectroscopy allows for an independent measurement of the vesicle's bending rigidity. Combining this bending rigidity with the radius of newly formed vesicles, which is determined by the ratio of bending rigidity and line tension, we can determine the line tension. We find that it is the line tension that controls the trend in size of the vesicles. In summary, this means that here one has a surfactant mixture that delivers well-defined vesicles, whose size is controlled by the electrostatic interactions of the head groups.

Bolaamphiphiles─amphiphilic molecules with polar groups at each of the two ends of a hydrophobic tail with pH-sensitive spontaneous molecular curvatures, endow membranes of extremophiles with an exquisite balance between stability (or robustness) and adaptability (or plasticity). But how the presence (or real-time insertion) of bolaamphiphiles influences lamellar lipid membranes is poorly understood. Using a combination of time-resolved confocal fluorescence microscopy, in situ small-angle X-ray and neutron scattering (SAXS and SANS), and neutron spin echo (NSE) measurements, we monitor here the pH-dependent interactions of nanoscopic vesicles of a representative bolaamphiphile─a glucolipid consisting of a single glucose headgroup and a C18:1 (oleyl) fatty acid tail (G-C18:1)─with the membranes of an essentially cylindrical fluid-phase phospholipid (dioleoylphosphatidylcholine, DOPC). We found that the two mesophases interact spontaneously at all pH values, producing large-scale morphological remodeling. Under neutral and acidic conditions, when the bolaamphiphile assumes a cylindrical shape, vesicles fuse with one another, producing invaginations, inner tubulation, and vesicle-in-vesicle aggregates. Under basic pH, by contrast, when the carboxylic acid is deprotonated and the molecule is inverted-conical in shape, the bolaamphiphile causes phospholipid membranes to undergo poration, budding, and vesiculation. This pH-dependent environmentally sensitive membrane remodeling without the disruption of the essential bilayer motif illustrates how local molecular-level packing perturbations can translate into global system-level morphological changes, enabling membranes to acquire environmental sensitivity and real-time adaptability. These results support the notion that molecular fluxes─which add (or remove) amphiphilic molecules to biological membranes─can endow de novo functionalities (e.g., pH sensitivity) and influence global morphologies of cell-sized vesicles.

We present a quantitative comparison of the dynamic structure factors from unentangled and strongly entangled poly(butylene oxide) (PBO) melts. As expected, the low molecular weight PBO displays Rouse dynamics, however, with very significant subdiffusive center-of-mass diffusion. The spectra from high molecular weight entangled PBO can be very well described by the dynamic structure factor based on the concept of local reptation, including the Rouse dynamics within the tube and allowing for non-Gaussian corrections. Comparing quantitatively the spectra from both polymers leads to the surprising result that their spectra differ only by the contribution of classical Rouse diffusion for the low molecular weight melt. The subdiffusive component is common for both the low and high molecular weight PBO melts, indicating that in both melts the same interchain potential is active, thereby supporting the validity of the Generalized Langevin Equation approach.

We consider the dynamic structure factor (DSF) of quasi-spherical vesicles and present a generalization of an expression that was originally formulated by Zilman and Granek (ZG) for scattering from isotropically oriented quasi-flat membrane plaquettes. The expression is obtained in the form of a multi-dimensional integral over the undulating membrane surface. The new expression reduces to the original stretched exponential form in the limit of sufficiently large vesicles, i.e., in the micron range or larger. For much smaller unilamellar vesicles, deviations from the asymptotic, stretched exponential equation are noticeable even if one assumes that the Seifert-Langer leaflet density mode is completely relaxed and membrane viscosity is neglected. To avoid the need for an exhaustive numerical integration while fitting to neutron spin echo (NSE) data, we provide a useful approximation for polydisperse systems that tests well against the numerical integration of the complete expression. To validate the new expression, we performed NSE experiments on variable-size vesicles made of a POPC/POPS lipid mixture and demonstrate an advantage over the original stretched exponential form or other manipulations of the original ZG expression that have been deployed over the years to fit the NSE data. In particular, values of the membrane bending rigidity extracted from the NSE data using the new approximations were insensitive to the vesicle radii and scattering wavenumber and compared very well with expected values of the effective bending modulus ( κ̃ ) calculated from results in the literature. Moreover, the generalized scattering theory presented here for an undulating quasi-spherical shell can be easily extended to other models for the membrane undulation dynamics beyond the Helfrich Hamiltonian and thereby provides the foundation for the study of the nanoscale dynamics in more complex and biologically relevant model membrane systems.

In this work, we investigate the effect of concentrated alcoholic solutions (up to 40%w) % w ) on extruded 1,2dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes using scattering techniques. Extrusion in alcoholic aqueous solutions (methanol, ethanol, or butanol) reduces liposome size, evidenced from the decrease in hydrodynamic radius (RH) R H ) obtained from dynamic light scattering. Short-chain alcohols such as ethanol and butanol soften the lipid membranes, as observed by the decrease of the unrelaxed bending modulus (x x ) obtained by neutron spin-echo spectroscopy. Thus, softer membranes are easily ruptured during extrusion, leading to a reduction in vesicle radius corroborated by a reduction in both RH H and radius of gyration as seen by dynamic and static light scattering. Moreover, model-free analysis of small-angle neutron scattering (SANS) curves suggests that solvent molecules become incorporated into the lipid membrane. Analysing deviations in the scattering invariant from values predicted by mass balance, we find that the volume fraction of liposomes increases, modifying the scattering length density of the assemblies. By quantifying these changes, we estimate that 12% to 18% of the liposome membrane is composed of solvent molecules (alcohol + water), depending on the type of alcohol and its concentration present in solution, with the exception of glycerol where next to no incorporation was observed. Finally, structural parameters obtained through light scattering and changes in contrast profiles calculated from analysis of the invariant were corroborated through modelling of the SANS curves. Modelling suggests that a reduction of bilayer thickness takes place for liposomes dispersed in ethanolic and butanolic solutions, but not in the presence of methanol or glycerol.

Ion-specific effects in aqueous solutions of polyelectrolytes are addressed here. We focus on ionene cationic chains, featuring simple structure, absence of side-groups and very regular chain charge density. Ion-specific effects in ionene solutions are demonstrated using a series of monovalent (halide) counterions. The study combines both static and dynamic measurements by small angle neutron scattering, neutron spin echo and PFG-NMR. Ion-specific effects are a phenomenon at high polyelectrolyte concentration and the nature of the counterion is seen to influence drastically the ionene chain-chain interactions. The origin lies in the closer approach of large, highly polarisable counterions to the chain backbone, leading to more constricted counterion clouds. Equally affected is the local chain rigidity, as well as collective and self-diffusion coefficients at larger scales. Small, nonpolarizable, strongly hydrating counterions, here F− ions, lead to locally rigid chains. For such chains, the nm-scale collective dynamics as seen by neutron spin echo, is the fastest, while the self-diffusion seen at μm scale by PFG-NMR is the slowest. In other words, the loss of charge on the chain due to ion-specific counterion ”condensation” has the opposite effect on collective diffusion and self-diffusion of the chains.

A confined bicontinuous C10E4-D2O-n-octane microemulsion is studied using neutron spin echo spectroscopy (NSE). Controlled pore glasses serve as confining matrices with pore diameters ranging from 24 to 112 nm. Firstly, the microemulsion in bulk is investigated by NSE and dynamic light scattering, which allows the determination of the unperturbed collective dynamics as well as the observation of the undulation of the surfactant film. In confinement, it is observed that the collective modes are drastically slowed down in all investigated pore sizes. The undulations of the surfactant film in the largest pores are found to be comparable to those of the bulk and decrease with decreasing pore diameter. Fitting procedures of the intermediate scattering function revealed that the long wavelength undulations are cut off from the spectrum of fluctuation modes due to the interactions with the pore walls.

Polyelectrolytes (PE) are polymeric macromolecules in aqueous solutions characterized by their chain topology and intrinsic charge in a neutralizing fluid. Structure and dynamics are related to several characteristic screening length scales determined by electrostatic, excluded volume, and hydrodynamic interactions. We examine PE dynamics in dilute to semidilute conditions using dynamic light scattering, neutron spinecho spectroscopy, and pulse field gradient NMR spectroscopy. We connect macroscopic diffusion to segmental chain dynamics, revealing a decoupling of local chain dynamics from interchain interactions. Collective diffusion is described within a colloidal picture, including electrostatic and hydrodynamic interactions. Chain dynamics is characterized by the classical Zimm model of a neutral chain retarded by internal friction. We observe that hydrodynamic interactions are not fully screened between chains and that the internal friction within the chain increases with an increase in ion condensation on the chain.

By combining oppositely charged polydiallyldimethylammonium chloride (PDADMAC) and sodium polyacrylate (NaPA), interpolyelectrolyte complexes (IPECs) can be formed in aqueous solution. Such IPECs are studied for rather short NaPA and under variation of the Mw of PDADMAC. The focus is on elucidating the effect of having a hydrophobic modification of the NaPA, which is introduced by having 10 mol% of the monomeric units substituted by ones carrying a dodecyl alkyl chain. This modification renders the complexes more hydrophobic, which is seen in the fact that precipitation of the complexes occurs at a lower mixing ratio and the biphasic region is also wider. The structures of the soluble IPECs are studied by a combination of light and neutron scattering (SANS). It is observed that the complexes formed possess typical radii of gyration of approximate to 30-40 nm, which become somewhat smaller with increasing length of the PDADMAC chain. The SANS data can be described well with the Beaucage model for complexes, where locally small hydrophobic domains of cylindrical shape are formed, whose persistence length decreases with increasing content of NaPA in the complexes. In contrast no such structures are seen for NaPA without the hydrophobic modification. The cylindrical domains are then arranged within larger-sized clusters of 30-40 nm, which become more compact with reduced length of the PDAMAC chains. The structure of the IPECs is largely determined by the presence of the hydrophobic modification of the NaPA and is further controlled by the length of the hydrophobic modification. Such IPECs of controlled structure, relatively small size, and containing hydrophobic domains are potentially interesting as delivery systems due to having domains of variable polarity.