Project description:Ion pair amphiphile (IPA), a lipid-like complex composed of a pair of cationic and anionic surfactants, has great potentials in various pharmaceutical applications. In this work, we utilized molecular dynamics (MD) simulation to systematically examine the structural and mechanical properties of the biomimetic bilayers consist of alkyltrimethyl-ammonium-alkylsulfate (CmTMA⁺-CnS-) IPAs with various alkyl chain combinations. Our simulations show an intrinsic one-atom offset for the CmTMA⁺ and CnS- alignment, leading to the asymmetric index definition of ΔC = m - (n + 1). Larger |ΔC| gives rise to higher conformational fluctuations of the alkyl chains with the reduced packing order and mechanical strength. In contrast, increasing the IPA chain length enhances the van der Waals interactions within the bilayer and thus improves the bilayer packing order and mechanical properties. Further elongating the CmTMA⁺-CnS- alkyl chains to m and n ≥ 12 causes the liquid disorder to gel phase transition of the bilayer at 298 K, with the threshold membrane properties of 0.45 nm² molecular area, deuterium order parameter value of 0.31, and effective bending rigidity of 20 kBT, etc. The combined results provide molecular insights into the design of biomimetic IPA bilayers with wide structural and mechanical characteristics for various applications.
Project description:Photocleavable protecting groups (PPGs) enable the precise spatiotemporal control over the release of a payload of interest, in particular a bioactive substance, through light irradiation. A crucial parameter that determines the practical applicability of PPGs is the efficiency of payload release, largely governed by the quantum yield of photolysis (QY). Understanding which parameters determine the QY will prove crucial for engineering improved PPGs and their effective future applications, especially in the emerging field of photopharmacology. The Contact Ion Pair (CIP) has been recognized as an important intermediate in the uncaging process, but the key influence of its fate on the quantum yield has not been explored yet, limiting our ability to design improved PPGs. Here, we demonstrate that the CIP escape mechanism of PPGs is crucial for determining their payload- and solvent-dependent photolysis QY, and illustrate that an intramolecular type of CIP escape is superior over diffusion-dependent CIP escape. Furthermore, we report a strong correlation of the photolysis QY of a range of coumarin PPGs with the DFT-calculated height of all three energy barriers involved in the photolysis reaction, despite the vastly different mechanisms of CIP escape that these PPGs exhibit. Using the insights obtained through our analysis, we were able to predict the photolysis QY of a newly designed PPG with particularly high accuracy. The level of understanding of the factors determining the QY of PPGs presented here will move the ever-expanding field of PPG applications forward and provides a blueprint for the development of PPGs with QYs that are independent of payload-topology and solvent polarity.
Project description:Without bioadhesive delivery devices, complex compounds are typically degraded or cleared from mucosal tissues by the mucous layer.While some chemically modified, microstructured surfaces have been studied in aqueous environments,adhesion due to geometry alone has not been investigated. Silicon nanowire-coated beads show significantly better adhesion than those with targeting agents under shear, and can increase the lift-off force 100-fold. We have shown that nanowire coatings, paired with epithelial physiology, significantly increase adhesion in mucosal conditions.
Project description:The development of cost-effective, biocompatible soft wound dressings is highly desirable; however, conventional dressings are only designed for flat wounds, which creates difficulty with promising healing efficiency in complex practical conditions. Herein, we developed a tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels composed of chemically crosslinked hyaluronic acid methacryloyl (HAMA) network and poly(N-hydroxyethyl acrylamide) (PHEAA) network rich in multiple hydrogen bonding. Due to the multiple chemical crosslinking sites (acrylamide groups) of HAMA; the bulk HEMA/PHEAA hydrogels presented significant enhancements in mechanical properties (∼0.45 MPa) than common hyaluronic acid hydrogels (<0.1 MPa). The abundant hydrogen bonding also endowed the resultant hydrogels with extremely high adhesiveness on many nonporous substrates, including glass and biological tissues (e.g., heart, liver, lung, kidney, stomach, and muscle), with a considerable interfacial toughness of ∼1432 J m-2. Accordingly, since both natural hyaluronic acid derivative polymers and hydrophilic PHEAA networks are highly biocompatible, the hydrogel matrix possesses good blood compatibility (<5% of hemolysis ratio) and satisfies the general dressing requirements (>99% of cell viability). Based on these physicochemical features, we have demonstrated that this adhesive hydrogel, administered in the form of a designed patch, could be applied to wound tissue healing by promoting epithelialization, angiogenesis, and collagen deposition. We believe that our proposed biomimetic hydrogel design holds great potential for wound repair and our developed HAMA/PHEAA hydrogels are extremely promising for the next-generation tissue healings in emergency situations.
Project description:Polydopamines (PDA) are a popular class of materials and promising candidates as adhesives for new fastening techniques. PDA layers can be formed on a wide range of substrates in various environments. Here, we present a novel method for functionalizing PDA-based copolymer films by using click chemistry. These copolymers adhere strongly to various surfaces and simultaneously have active groups that allow the attachment of functional groups. We discuss the coupling of two types of chitosan and a rhodamine B dye molecule to the alkyne groups of the copolymers by employing click reactions. Azidopropyl methacrylate (AzMA), methyl methacrylate (MMA), and dopamine methacrylamide (DOMA) are copolymerized and codeposited with (3-aminopropyl)triethoxysilane on silicon wafers, polyethylene (PE), and polytetrafluoroethylene (PTFE). AzMA provides the surfaces with azides for use in click reactions, MMA functions to control the polymer as a nonfunctional diluent, whereas DOMA provides adhesion, as well as cross-linking groups. After codeposition, the dyes are grafted to the copolymer to illustrate the ability of the films to link functional groups covalently. Fourier transform infrared spectroscopy confirms the successful click reaction in solution, and atomic force microscopy shows the surface morphologies following grafting. Fluorescence microscopy provides evidence of successful grafting. As an example of a possible application, layers exhibiting antifouling properties are prepared. Chitosan grafted to PE is tested for antifouling performance. These functionalized layers show nonspecific inhibition of protein adsorption. We find that chitosan can lower the adsorption of fluorescein-labeled bovine serum albumin (BSA) protein by more than 90% for the best performing fluorescein-labeled BSA protein and by more than 90% for the best-performing layer. These results demonstrate the viability of our PDA-based copolymers for surface functionalization through click chemistry grafting at challenging adhesion to surfaces.
Project description:In this study, we evaluated bioinspired adhesive primers for durable adhesion between dentin and composite resins. N-3,4-Dihydroxyphenethyl methacrylamide (DMA) primer monomer (small bifunctional group molecules containing catechol and acrylic groups at opposite ends) was prepared to mimic the interaction between the catechol group and the mineral interface of marine mussels. The shear bonding strength, microleakage, degree of conversion, contact angle, and compatibility were tested. The shear bond strength was significantly improved, and microleakage was diminished after the application of the DMA primer. However, the degree of conversion was decreased. The wettability of the dentin was enhanced, and the DMA primer showed no negative influence on cell proliferation. The results of this study showed the possibility of using DMA primers in clinical practice. This may provide a new strategy for improving adhesion durability.
Project description:Polyampholytes (PA) are a special class of polymers comprising both positive and negative monomers along their sequence. Most proteins have positive and negative residues and are PAs. Proteins have a well-defined sequence while synthetic PAs have a random charge sequence. We investigated the translocation behavior of random polyampholyte chains through a pore under the action of an electric field by means of Monte Carlo simulations. The simulations incorporated a realistic translocation potential profile along an extended asymmetric pore and translocation was studied for both directions of engagement. The study was conducted from the perspective of statistics for disordered systems. The translocation behavior (translocation vs. rejection) was recorded for all 220 sequences comprised of N = 20 charged monomers. The results were compared with those for 107 random sequences of N = 40 to better demonstrate asymptotic laws. At early times, rejection was mainly controlled by the charge sequence of the head part, but late translocation/rejection was governed by the escape from a trapped state over an antagonistic barrier built up along the sequence. The probability distribution of translocation times from all successful attempts revealed a power-law tail. At finite times, there was a population of trapped sequences that relaxed very slowly (logarithmically) with time. If a subensemble of sequences with prescribed net charge was considered the power-law decay was steeper for a more favorable net charge. Our findings were rationalized by theoretical arguments developed for long chains. We also provided operational criteria for the translocation behavior of a sequence, explaining the selection by the translocation process. From the perspective of protein translocation, our findings can help rationalize the behavior of intrinsically disordered proteins (IDPs), which can be modeled as polyampholytes. Most IDP sequences have a strong net charge favoring translocation. Even for sequences with those large net charges, the translocation times remained very dispersed and the translocation was highly sequence-selective.
Project description:Antifreeze proteins from polar fish species are potent ice recrystallization inhibitors (IRIs) effectively stopping all ice growth. Additives that have IRI activity have been shown to enhance cellular cryopreservation with potential to improve the distribution of donor cells and tissue. Polyampholytes, polymers with both anionic and cationic side chains, are a rapidly emerging class of polymer cryoprotectants, but their mode of action and the structural features essential for activity are not clear. Here regioregular polyampholytes are synthesized from maleic anhydride copolymers to enable stoichiometric installation of the charged groups, ensuring regioregularity, which is not possible using conventional random copolymerization. A modular synthetic strategy is employed to enable the backbone and side chain hydrophobicity to be varied, with side chain hydrophobicity found to have a profound effect on the IRI activity. The activity of the regioregular polymers was found to be superior to those derived from a standard random copolymerization with statistical incorporation of monomers, demonstrating that sequence composition is crucial to the activity of IRI active polyampholytes.
Project description:We report a rotaxane based on a simple urea motif that binds Cl- selectively as a separated ion pair with H+ and reports the anion binding event through a fluorescence switch-on response. The host selectively binds Cl- over more basic anions, which deprotonate the framework, and less basic anions, which bind more weakly. The mechanical bond also imparts size selectivity to the ditopic host.
Project description:Silk has emerged as an interesting candidate among protein-based nanocarriers due to its favorable properties, including biocompatibility and a broad spectrum of processing options to tune particle critical quality attributes. The silk protein conformation during storage in the middle silk gland of the silkworm is modulated by various factors, including the most abundant metallic ion, calcium ion (Ca2+). Here, we report spiking of liquid silk with calcium ions to modulate the silk nanoparticle size. Conformational and structural analyses of silk demonstrated Ca2+-induced silk assemblies that resulted in a liquid crystalline-like state, with the subsequent generation of β-sheet-enriched silk nanoparticles. Thioflavin T studies demonstrated that Ca2+ effectively induces self-assembly and conformation changes that also increased model drug loading. Ca2+ incorporation in the biopolymer feed significantly increased the nanoparticle production yield from 16 to 89%, while simultaneously enabling Ca2+ concentration-dependent particle-size tuning with a narrow polydispersity index and altered zeta potential. The resulting silk nanoparticles displayed high biocompatibility in macrophages with baseline levels of cytotoxicity and cellular inflammation. Our strategy for manufacturing biomimetic silk nanoparticles enabled overall tuning of particle size and improved yields─features that are critical for particle-based nanomedicines.