The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6^(*) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6^(*) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions.

Sessile marine mussels must “dry” underwater surfaces before adhering to them. Synthetic adhesives have yet to overcome this fundamental challenge. Previous studies of bioinspired adhesion have largely been performed under applied compressive forces, but such studies are poor predictors of the ability of an adhesive to spontaneously penetrate surface hydration layers. In a force‐free approach to measuring molecular‐level interaction through surface‐water diffusivity, different mussel foot proteins were found to have different abilities to evict hydration layers from surfaces—a necessary step for adsorption and adhesion. It was anticipated that DOPA would mediate dehydration owing to its efficacy in bioinspired wet adhesion. Instead, hydrophobic side chains were found to be a critical component for protein–surface intimacy. This direct measurement of interfacial water dynamics during force‐free adsorptive interactions at solid surfaces offers guidance for the engineering of wet adhesives and coatings.

We present experimental evidence for the significant effect that water can have on the functional structure of proteins in solution. Human (HSA) and Bovine Serum Albumin (BSA) have an amino acid sequence identity of 75.52% and are chosen as model proteins. We employ EPR-based nanoscale distance measurements using double electron-electron resonance (DEER) spectroscopy and both albumins loaded with long chain fatty acids (FAs) in solution to globally (yet indirectly) characterize the tertiary protein structures from the bound ligands’ points of view. The complete primary structures and crystal structures of HSA and as of recently also BSA are available. We complement the picture as we have recently determined the DEER-derived solution structure of HSA and here present the corresponding BSA solution structure. The characteristic asymmetric FA distribution in the crystal structure of HSA can surprisingly be observed by DEER in BSA in solution. This indicates that the BSA conformational ensemble in solution seems to be narrow and close to the crystal structure of HSA. In contrast, for HSA in solution a much more symmetric FA distribution was found. Thus, conformational adaptability and flexibility dominate in the HSA solution structure while BSA seems to lack these properties. We further show that differences in amino acid hydropathies of specific structural regions in both proteins can be used to correlate the observed difference in the global (tertiary) solution structures with the differences on the primary structure level.

Ionic liquids (ILs) feature a variety of properties that make them a unique class of solvents. To gain a better understanding of how ILs solvate compounds of different chemical structure, we used pulsed high-field electron paramagnetic resonance (EPR) spectroscopy at W-band (∼94 GHz) and continuous wave EPR at X-band (∼9.4 GHz) on three TEMPO-based spin probes with different substitutions at the 4-position: 4-R-2,2,6,6-tetramethylpiperidine-1-oxyl, with R = N(CH₃)₃ ⁺, Cat-1, R = COO ⁻, TEMPO-4-carboxylate, and R = OH, TEMPOL. The spin probes are dissolved in imidazolium based ILs with different alkyl chain lengths (–C₂H₅, –C₄H₉, –C₆H₁₃) and anions (BF₄ ⁻, PF₆ ⁻) and also in molecular solvents (methanol, water–glycerol). X-Band EPR at RT shows that the reorientational motion of the charged spin probes in ILs is about fivefold slower than that of the TEMPOL. Moreover, anion variation from BF₄ ⁻ to PF₆ ⁻ in ILs most strongly slows down the rotational motion (as measured by the rotational correlation time τ_r ) of Cat-1, followed by TEMPOL, while τ_r of TEMPO-4-carboxylate is least affected. The EPR parameters g_xx and A_zz (tensor elements of the g- and hyperfine tensor) are sensitive to environmental effects and are only fully resolved at the high field used in this study. Changes of g_xx and A_zz values of the Cat-1 in ILs and methanol are very small especially compared to that of TEMPO-4-carboxylate, indicating that Cat-1 is located in a polar region of the ILs resembling the situation in methanol. On the other hand, the g_xx value of TEMPO-4-carboxylate is sensitive to the length of alkyl group which shows that TEMPO-4-carboxylate is close to the nonpolar region of ILs. The small differences in the chemical substitution of the spin probes used here are sufficient for the molecules to reside in different domains of different dielectric properties in ILs. Our combined results are in good agreement with a picture of a nanophase separation, in which the charged cations and anions form polar regions and the hydrophobic alkyl chains of the IL cations form non-polar regions.

X-ray absorption and x-ray magnetic circular dichroism (XMCD) spectra have been recorded at the Pt $L_{2,3}$ edges of ${\text{Pt}}_{13}$ and hydrogenated ${\text{Pt}}_{13}{\text{H}}_m$ clusters dispersed in NaY zeolite. A Pt foil was also measured as reference for comparison with bulk Pt. From the x-ray absorption near edge structure measurements the average number of holes $n_h$ in the $5d$ band of these systems is found. In the ${\text{Pt}}_{13}{\text{H}}_m$ sample the Pt-H antibonding state increases $n_h$ with respect to the ${\text{Pt}}_{13}$ sample. It gives rise to a shape resonance with energy $E_{\text{res}}=2.3\text{eV}$. The average orbital and spin moments $m_L$ and $m_S$ for the Pt atom have been determined from the XMCD measurements. The total magnetic-moment field dependence XMCD($H$) was determined and scaled to the absolute value of the average moment per Pt atom. The fit of XMCD($H$) to a Langevin function yields a magnetic moment per cluster of $\mu =3.7\pm 0.4$ and $3.0\pm 0.4{\mu }_{\text{B}}$, for ${\text{Pt}}_{13}$ and ${\text{Pt}}_{13}{\text{H}}_m$, respectively. It is shown that nonmagnetic clusters coexist with those giving magnetic signal. The amount of Pt constituting the magnetic ${\text{Pt}}_{13}$ clusters is 15–20% of the total Pt content. The XMCD data are compared with superconducting quantum interference device magnetization measurements. The moment found indicates that the cluster spin of ${\text{Pt}}_{13}$ and ${\text{Pt}}_{13}{\text{H}}_m$ is in the range $S\approx 2–3$. They are compared to predictions calculated by density-functional methods.