Transmembrane ion channels frequently regulate ion permeation by forming bundle crossing of the pore-lining helices when deactivated. The resulting physical constriction is believed to serve as the de facto gate that imposes the major free energy barrier to ion permeation. Intriguingly, many ion channels also contain highly hydrophobic inner pores enclosed by bundle crossing, which can undergo spontaneous dewetting and give rise to a \"vapor barrier\" to block ion flow even in the absence of physical constriction. Using atomistic simulations, we show that hydrophobic gating and bundle-crossing mechanisms co-exist and complement one and another in the human TRPV4 channel. In particular, a single hydrophilic mutation in the lower pore can increase pore hydration and reduce the ion permeation free energy barrier by about half without affecting the bundle crossing. We believe that hydrophobic gating may play a key role in other bundle-crossing ion channels with hydrophobic inner pores.

We analyze modularity for a B-M-E triblock protein designed to self-assemble into antifouling coatings. Previously, we have shown that the design performs well on silica surfaces when B is taken to be a silica-binding peptide, M is a thermostable trimer domain, and E is the uncharged elastin-like polypeptide (ELP), E = (GSGVP)40. Here, we demonstrate that we can modulate the nature of the substrate on which the coatings form by choosing different solid-binding peptides as binding domain B and that we can modulate antifouling properties by choosing a different hydrophilic block E. Specifically, to arrive at antifouling coatings for gold surfaces, as binding block B we use the gold-binding peptide GBP1 (with the sequence MHGKTQATSGTIQS), while we replace the antifouling blocks E by zwitterionic ELPs of different lengths, EZn = (GDGVP-GKGVP)n/2, with n = 20, 40, or 80. We find that even the B-M-E proteins with the shortest E blocks make coatings on gold surfaces with excellent antifouling against 1% human serum (HS) and reasonable antifouling against 10% HS. This suggests that the B-M-E triblock protein can be easily adapted to form antifouling coatings on any substrate for which solid-binding peptide sequences are available.

Pistia stratiotes is an aquatic plant with a complex structure that allows it to stay afloat. It grows quickly, and in large numbers becomes an undesirable plant as an invasive species. Describing the dynamics of a water drop splash on P. stratiotes leaves can contribute to increasing knowledge of its behavior and finding alternative methods for eradicating it or using it for the benefit of the environment. The non-wettable surface of P. stratiotes presents a complex structure-simple uniseriate trichomes and also ridges and veins. We analyzed the drop impact on a leaf placed on the water surface and recorded it by high-speed cameras. Based on the recordings, quantitative and qualitative analyses were performed. After impacting the leaf, the water drop spread until it reached its maximum surface area accompanied by the ejection of early droplets in the initial stage. Thereafter, three scenarios of water behavior were observed: (i) drop receding and stabilization; (ii) drop receding and ejection of late droplets formed in the later stage as an effect of elastic deformation of the leaf; and (iii) drop breaking apart and ejection of late droplets. The results indicated that the increasing kinetic energy of the impacting drops expressed by the Weber number and the complex leaf surface have an effect on the course of the splash. The simple uniseriate trichomes of the P. stratiotes leaf and the high energy of the falling drops were responsible for the formation and characteristics of the early droplets. The presence of ridges and veins and the leaf\'s mechanical response had an impact on the occurrence of late droplets.

In this work, the behavior of four different commercially available polarizing agents is investigated employing the non-ionic model surfactant 1-octanol as analyte. A relative method for the comparison of the proportion of the direct and indirect polarization transfer pathways is established, allowing a direct comparison of the polarization efficacy for different radicals and different parts of the 1-octanol molecule despite differences in radical concentration or sample amount. With this approach, it could be demonstrated that the hydrophilicity is a key factor in the way polarization is transferred from the polarizing agent to the analyte. These findings are confirmed by the determination of buildup times Tb, illustrating that the choice of polarizing agent plays an essential role in ensuring an optimal polarization transfer and therefore the maximum amount of enhancement possible for DNP enhanced NMR measurements.

Highly ordered, straight amyloid fibrils readily lend themselves to structure determination techniques and have therefore been extensively characterized. However, the less ordered curly fibrils remain relatively understudied, and the structural organization underlying their specific characteristics remains poorly understood. We found that the exemplary curly fibril-forming protein ovalbumin contains multiple aggregation prone regions (APRs) that form straight fibrils when isolated as peptides or when excised from the full-length protein through hydrolysis. In the context of the intact full-length protein, however, the regions separating the APRs facilitate curly fibril formation. In fact, a meta-analysis of previously reported curly fibril-forming proteins shows that their inter-APRs are significantly longer and more hydrophobic when compared to straight fibril-forming proteins, suggesting that they may cause strain in the amyloid state. Hence, inter-APRs driving curly fibril formation may not only apply to our model protein but rather constitute a more general mechanism.

Hydrophilic polymer embolism (HPE) is a rare iatrogenic complication of the use of polymer-coated intravascular devices, which may affect several organ systems including the skin. Herein, we present a patient who developed a cutaneous eruption with associated neurologic manifestations secondary to localized HPE. This is a potentially underdiagnosed, life-threatening complication and physicians should consider HPE when evaluating skin eruptions in patients who have undergone endovascular procedures.

Natural aglycones, a major ingredient accompanied by glycosides in plants, have played an important role in the treatment of various diseases. However, their bioavailability is limited by their poor water solubility. In contrast to previous efforts that required the use of new exotic materials which may raise concerns about biocompatibility, we report the first case of excipient-free nanodispersions in which an insoluble glycyrrhetinic acid (GA) assembled with its amphiphilic parent drug diammonium glycyrrhizinate (DG) into water-dispersible nanodispersions (130.8 nm for particle size and 91.74% for encapsulation efficiency). This strategy largely increased GA\'s water apparent solubility by hundreds of times to 549.0 μg/mL with a high cumulative dissolution percentage in vitro greater than 80% in 5 min. The study on the formation mechanism showed that the OH, C-O and C=O group stretching peaks shifted in the FTIR spectra of GA-DG nanodispersions, while the COOH peak (δ COOH 12.19 ppm) disappeared in the 1H NMR spectrum of GA-DG nanodispersions, indicating that carboxyl groups on GA may interact with the hydroxyl groups of DG in solution. Molecular dynamics simulations suggested that both hydrophobic interactions and hydrogen-bond interactions contribute to the coassembly of GA and DG molecules in aqueous solution. Oral pharmacokinetic studies in rats demonstrated that such nanodispersions have a significant increase in Cmax and AUC0-t of 2.45- and 3.45-fold compared with those for GA, respectively. Therefore, this strategy, employing amphiphilic glycosides as excipients to prepare nanodispersions, not using new materials, paves the way for the further application of hydrophobic aglycone drugs.

Lipid mesophases are able to incorporate and release a plethora of molecules, spanning from hydrophobic drugs to small hydrophilic proteins and therefore they have been widely used as drug delivery systems. However, their 3-5 nm water channels do not allow the release of large hydrophilic molecules such as monoclonal antibodies and therapeutic proteins. To overcome this major geometrical constraint, we designed a gel by mixing monoacylglycerol lipids, generally recognized as safe for human and/or animal use by FDA, and phospholipids, to obtain a material with swollen water channels suitable to host and further release macromolecules. Apoferritin, a 12 nm nanocage protein with intrinsic tumor-targeting properties able to incorporate several molecules, was selected here as the hydrophilic model protein to be embedded in the biocompatible gel. When immersed completely in the release media, mesophases with a swollen water channel of 22 nm, composed of monoolein and doped with 5 mole% of DOPS and 10 mole% of Chol allowed us to achieve a protein release of 60%, which is 120 times higher with respect to that obtained by employing non swollen-LMPs composed only of monoolein. Thus, the formulation can be administered locally to the rectal or vaginal mucosa, reducing the drawbacks often associated with the parenteral administration of bio-therapeutics. This approach would pave the way for the local application of other biomacromolecules (including human ferritin, monoclonal antibodies and antibody drug-conjugates) in those diseases easily reachable by a local application such as rectal or vaginal cancer.

Carbon nanotubes (CNTs) are one of the unique and promising nanomaterials that possess plenty of applications, such as biosensors, advanced drug delivery systems and biotechnology. CNTs bind rapidly with proteins, which result in the formation of a protein coating layer known as a \"protein corona\" around the surface of the nanomaterial. This hinders their applications as a drug carrier and influences the properties of biological macromolecules. The present work focuses on studying the thermal stability and molecular level interactions of two heme proteins, hemoglobin (Hb) and myoglobin (Mb), in the presence of carboxylated functionalized multi-walled CNTs (CA-MWCNTs). Through the current study, the following steps have been taken to distinguish the biocompatibility of the hydrophilic surface CA-MWCNTs for heme proteins via a series of spectroscopic techniques and differential scanning calorimetry (DSC). UV-Visible and steady-state fluorescence spectroscopy were used to reveal changes in the aromatic amino acid residues of heme proteins upon the addition of CA-MWCNTs. Circular dichroism spectroscopy (CD) shows the alteration in the native structure of proteins in the presence of the nanomaterial. A tremendous increase in the size of the protein CA-MWCNTs system is observed in dynamic light scattering (DLS), which clearly manifests the protein corona formation. Unexpectedly, both proteins interact differently with CA-MWCNTs, which is observed in CD spectroscopy and DSC. In the presence of CA-MWCNTs, an increase in the transition temperature (Tm) was observed for Hb, while the Tm value decreases for Mb. Different interactions with proteins at the molecular scale may be the reason for this unexpected behavior. Henceforth, the present results can help in the design of the next-generation drug carrier nanomaterials with the idea of the heme protein corona formation prior to development.

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