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In recent years, the underlying mechanism of formation of the lipid corona and its stability have begun to garner interest in the nanoscience community. However, until now, very little is known about the role of different properties of nanoparticles (NPs) (surface charge density, hydrophobicity, and size) in lipid corona formation. Apart from the physicochemical properties of NPs, the different properties of lipids remain elusive in lipid corona formation. In the present contribution, we have investigated the interaction of phenylalanine-functionalized gold NPs (Au-Phe NPs) with different zwitterionic lipid vesicles of different phase states (sol–gel and liquid crystalline at room temperature) as a function of lipid concentration. The main objective of the present work is to understand how the lipid phase affects lipid corona formation and lipid-induced aggregation in various media. Our results establish that the lipid phase state, area per lipid head group, and the buffer medium play important roles in lipid-induced aggregation. The lipid corona occurs for NPs at high lipid concentration, irrespective of the phase states and area per lipid head group of the lipid bilayer. Notably, the lipid corona also forms at a low concentration of lipid vesicles in the liquid crystalline phase (1,2-dioleoyl-sn-glycero-3-phosphocholine). The corona formation brings in remarkable stability to NPs against freeze–thaw cycles. Based on the stability, for the first time, we classify lipid corona as “hard lipid corona” and “soft lipid corona”. This distinct classification will help to develop suitable nanomaterials for various biomedical applications.

Antibodies are recognition molecules that can bind to diverse targets ranging from pathogens to small analytes with high binding affinity and specificity, making them widely employed for sensing and therapy. However, antibodies have limitations of low stability, long production time, short shelf life, and high cost. Here, we report a facile approach for the design of luminescent artificial antibodies with nonbiological polymeric recognition phases for the sensitive detection, rapid identification, and effective inactivation of pathogenic bacteria. Transition-metal dichalcogenide (TMD) nanosheets with a neutral dextran phase at the interfaces selectively recognized S. aureus, whereas the nanosheets bearing a carboxymethylated dextran phase selectively recognized E. coliO157:H7 with high binding affinity. The bacterial binding sites recognized by the artificial antibodies were thoroughly identified by experiments and molecular dynamics simulations, revealing the significance of their multivalent interactions with the bacterial membrane components for selective recognition. The luminescent WS2artificial antibodies could rapidly detect the bacteria at a single copy from human serum without any purification and amplification. Moreover, the MoSe2artificial antibodies selectively killed the pathogenic bacteria in the wounds of infected mice under light irradiation, leading to effective wound healing. This work demonstrates the potential of TMD artificial antibodies as an alternative to antibodies for sensing and therapy.

Zwitterionic polymers have extraordinary properties, that is, significant hydration and the so-called antipolyelectrolyte effect, which make them suitable for biomedical applications. The hydration induces an antifouling effect, and this has been investigated significantly. The antipolyelectrolyte effect refers to the extraordinary ion-responsive behavior of particular polymers that swell and hydrate considerably in physiological solutions. This actuation begins to attract attention to achieve in vivoantifouling that is challenging for general polyelectrolytes. In this study, we established the sophisticated cornerstone of the antipolyelectrolyte effect in detail, including (i) the essential parameters, (ii) experimental verifications, and (iii) effect of improving antifouling performance. First, we find that both osmotic force and charge screening are essential factors. Second, we identify the antipolyelectrolyte effect by visualizing the swelling and hydration dynamics. Finally, we verify that the antifouling performance can be enhanced by exploiting the antipolyelectrolyte effect and report reduction of 85% and 80% in exand in vivobiofilm formation, respectively.

Single-walled carbon nanotube (SWCNTs-P)–small organic molecule hybrid materials are promising candidates for achieving high thermoelectric (TE) performance. In this study, we synthesized rod-coil amphiphilic molecules, that is, tri(ethylene oxide) chain-attached bis(bithiophenyl)-terphenyl derivatives (1and 2). Supramolecular functionalization of SWCNTs-Pwith 1or 2induced charge-transfer interactions between them. Improved TE properties of the supramolecular hybrids (SWCNTs-1and SWCNTs-2) are attributed to increased charge-carrier concentration (electrical conductivity), interfacial phonon scattering (thermal conductivity), and energy difference between the transport and Fermi levels (ETr– EF; Seebeck coefficient). SWCNTs-2exhibited a ZT of 0.42 × 10–2at 300 K, which is 350% larger than that of SWCNTs-P. Furthermore, 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ)-doped SWCNTs-2showed the highest ZT value of 1.96 × 10–2at 300 K among SWCNTs-P/small organic molecule hybrids known until now. These results demonstrated that the supramolecular functionalization of SWCNTs-Pwith small organic molecules could be useful for enhancement of TE performance and applications in wearable/flexible thermoelectrics.

In the medical industry, zwitterionic brushes have received significant attention owing to their antifouling effect that arose from their hydration ability. However, sufficient understanding of the hydration dynamics of zwitterionic brushes is required to fabricate the precisely controlled antifouling medical devices. In this paper, we successfully show that hydration, the interaction between water molecules and zwitterionic brushes, and its dynamics can be evaluated logically and quantitatively using (i) water contact angle, (ii) molecular dynamics simulation, and (iii) Raman spectroscopy. Based on the intuitive results on hydration, we precisely optimized the antifouling property of the model medical device, a removable orthodontic retainer, with various grafting efficiencies of 2-methacryloyloxyethyl phosphate choline. As a result, the model device reduced nonspecific adsorption of proteins and bacteria, indicating an improved antifouling effect, and also inhibited the formation of a biofilm. Furthermore, the device showed excellent physical properties desirable for application in the orthodontic field, meaning the balance between the antibacterial property and mechanical strength.

Various types of biological and synthetic nanopores have been developed and utilized for the high-throughput investigation of individual biomolecules. Biological nanopores made with channel proteins are so far superior to solid-state ones in terms of sensitivity and reproducibility. However, the performance of a biological nanopore is dependent on the protein in the channel structure its dimensions are predetermined and are difficult to modify for broader applications. Here inspired by the cytotoxic mechanisms of a saponin derivative, alpha-hederin, we report a nonproteinaceous nanopore that can be formed spontaneously in a lipid membrane. We propose the pore-forming mechanism of alpha-hederin in a cholesterol-rich lipid membrane and a strategy to control the pore-forming rate by a lipid partitioning method. The small diameter and effective thickness of alpha-hederin nanopores enabled us to discriminate ssDNA homopolymers as well as four types of nucleotides, showing its potential as a DNA sequencing tool.

Controlling the self-assembly behavior of caged proteins expands their potential applications in nanotechnology. While the structure of a caged E2 protein from pyruvate dehydrogenase is inert to any pH change, the incorporation of switchable GALA peptide that undergoes a coil-to-helix transition at acidic pH modulates its self-assembly property. By substituting the native α-helix at the C-terminus of the E2 protein with the GALA peptide, we report the first engineered caged protein with reversible inversed pH-responsive behavior. The redesigned caged E2 protein assumes an assembly profile that is distinct from the native state; it disassembles at pH 7.0 and self-assembles at pH 4.0 in a reversible manner. This unique reversible pH trigger suggests the applicability of the self-assembly control on other multi-subunit macromolecules.

Single-walled carbon nanotubes (SWNTs) covalently or noncovalently modified with polyethylene glycol (PEG) of different sizes (Mw= 550, 2000, 5000, and 7000) and grafting densities (5–16 PEGs per SWNT) were simulated using coarse-grained force fields. The covalently grafted PEGs are evenly distributed on SWNTs, while the noncovalently PEGylated SWNTs show the random distribution of PEGylated lipids adsorbed to the SWNT, in which the SWNT sidewall is less completely wrapped by PEGs and thus largely exposed to water, as was observed in experiments. For covalently PEGylated SWNTs, longer PEG chains with higher grafting density yield a larger size, more isotropic shape, and lower diffusivity of the SWNT–PEG complex. In particular, at low grafting density, the thickness of the PEG layer on SWNTs nearly equals the size of the mushroom, where the end-to-end distance of PEGs is smaller than the distance between the grafting points, similar to the conformation of an isolated chain in water. However, at high grafting density, the thickness of the PEG layer increases beyond the mushroom regime, indicating a mushroom-to-brush transition, in agreement with the Alexander–de Gennes theory. These findings indicate that the PEGylation method influences the distribution of PEG chains on SWNTs and that the PEG size and grafting density modulate the conformation of the conjugated PEG chains, which helps explain the experimentally proposed transition of the PEG conformation between mushroom and brush.

Self-assemblies of mixtures of a single-walled carbon nanotube (SWNT) and lipids were simulated using coarse-grained (CG) force fields previously developed and parametrized in this work. For lipids, lysophospholipids (single tail) and phospholipids (double tails) are ungrafted or grafted with poly(ethylene glycol) (PEG) at different sizes. In all simulated systems, lipids self-assemble along the SWNT, but their final conformations significantly differ. Simulations show that lysophospholipids helically wrap the SWNT as the “half-cylinder” conformation, which have been proposed by experiments but not captured by previous simulations. Phospholipids show “cylindrical micelles”, indicating the effect of the number of tails on the assembled structure. For both lysophospholipids and phospholipids, PEGylated lipids induce either “hemimicelle” or “random-adsorption” conformation, indicating dependence on the size of the lipid headgroup, because PEG chains with mushroom (solution-like) state induce the lipid-layer curvature and make lipids away from their neighbors. The number of lipids adsorbed onto SWNT increases stepwise as functions of time, implying that lipids self-assemble to their own aggregate in water modulated by the lipid headgroup and tail structure, and then the assembled lipids adsorb onto the SWNT surface. These results suggest important possible effects of PEGylation and lipid types on the self-assembled structure and mechanism, which compare favorably with experimental findings but also need to be further confirmed.

We performed molecular dynamics (MD) simu-lations of 36 copies of unmodified (charged), acetylated, and polyethylene glycol (PEG)-conjugated G4 dendrimers in dimyristoylphosphatidylcholine (DMPC) bilayers with explicit water using coarse-grained (CG) lipid and PEG force fields (FF). Attachment of small PEG chains to the dendrimer leads to the same reduction in membrane permeability as does attachment of acetyl groups, while a larger PEG size or a higher degree of PEGylation induces even fewer pores. This indicates that PEGylation is more efficient than acetylation in reducing membrane permeability and cytotoxicity, in qualitative agreement with experimental findings (Kim et al. Bioconjugate Chem. 2008, 19, 1660). Attachment of larger PEG chains makes the dendrimer−PEG complex larger and more spherical. Although a larger size and a more spherical shape are usually conducive to pore formation, a thick PEG layer on the dendrimer surface blocks the charge interaction between cationic dendrimer terminals and anionic lipid phosphate groups, and thus inhibits pore formation, despite the increased dendrimer size. Large PEG chains also keep the dendrimer−PEG complexes far from each other, suppressing interparticle aggregation.

Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8–10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation.

A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers of polyethylene oxide (PEO) and 27-mers of polyethylene glycol (PEG) in water based on C35r yield a persistence length λ=3.7Å, in quantitative agreement with experimentally obtained values of 3.7Å for PEO and 3.8Å for PEG; agreement with experimental values for hydrodynamic radii of comparably sized PEG is also excellent. The exponent υ relating the radius of gyration and molecular weight (Rg∝Mwυ) of PEO from the simulations equals 0.515±0.023, consistent with experimental observations that low molecular weight PEG behaves as an ideal chain. The shape anisotropy of hydrated PEO is 2.59:1.44:1.00. The dimension of the middle length for each of the polymers nearly equals the hydrodynamic radius Rh obtained from diffusion measurements in solution. This explains the correspondence of Rh and Rp, the pore radius of membrane channels: a polymer such as PEG diffuses with its long axis parallel to the membrane channel, and passes through the channel without substantial distortion.

We have performed molecular dynamics simulations of multiple copies of the lung-surfactant peptide SP-B1-25 in a palmitic acid (PA) monolayer. SP-B1-25 is a shorter version of lung-surfactant protein B, an important component of lung surfactant. Up to 30ns simulations of 20wt % SP-B1-25 in the PA monolayers were performed with different surface areas of PA, extents of PA ionization, and various initial configurations of the peptides. Starting with initial peptide orientation perpendicular to the monolayer, the predicted final tilt angles average 54°∼ 62° with respect to the monolayer normal, similar to those measured experimentally by Lee et al. (Biophysical Journal. 2001. Synchrotron x-ray study of lung surfactant-specific protein SP-B in lipid monolayers. 81:572–585). In their final conformations, hydrogen-bond analysis and amino acid mutation studies show that the peptides are anchored by hydrogen bond interactions between the cationic residues Arg-12 and Arg-17 and the hydrogen bond acceptors of the ionized PA headgroup, and the tilt angle is affected by the interactions of Tyr-7 and Gln-19 with the PA headgroup. Our work indicates that the factors controlling orientation of small peptides in lipid layers can now be uncovered through molecular dynamics simulations.

All-atom molecular dynamics simulations of the 10 nm-sized anionic polystyrene (PS) particle complexed with plasma proteins (human serum albumin, immunoglobulin gamma-1 chain-C, and apolipoprotein A-I) adsorbed onto lipid bilayers [asymmetrically composed of extracellular (zwitterionic) and cytosolic (anionic) leaflets] are performed. Free energies calculated from umbrella sampling simulations show that proteins on the particle more weakly bind to the zwitterionic leaflet than do bare particles, in agreement with experiments showing the suppression of the particle–bilayer binding by protein corona. Proteins on the particle interact more strongly with the anionic leaflet than with the zwitterionic leaflet because of charge interactions between cationic protein residues and anionic lipid headgroups, to an extent dependent on various plasma proteins. In particular, hydrogen bonds between proteins and zwitterionic leaflets restrict the motion of lipids and thus reduce the lateral dynamics of bilayers, while the tight binding between proteins and anionic leaflets disrupts the helical structure of proteins and disorders lipids, leading to an increase in the lateral dynamics of bilayers. These findings help explain the experimental observation regarding the fact that the bilayer dynamics decreases when interacting with protein corona and suggest that the effect of protein corona on the binding strength and bilayer dynamics depends on protein types and bilayer charges.

Multilayered nanofilm fabricating system with inkjet printing is developed by Jinkee Hong and co‐workers in article number 1700216. Inkjet printed nanofilms are composed of polymeric materials and bioactive materials, especially with enhanced structural stability of growth factor (basic Fibroblast Growth Factor). Growth factors containing nanofilms are effective in maintaining undifferentiated pluripotent stem cells by promoting proliferation and expansion.

Biologically versatile basic fibroblast growth factor (bFGF), well known for roles of signaling molecules between cells and regulating various cellular processes, has been proven to utilize specific functionalities. However, the remarkable functions are inclinable to dwindle with decrease of bFGFs' activity. In nanoscale, developing thin films with intrinsic characteristics of building molecules can facilitate handling various materials for desired purposes. Fabricating nanofilm and handling sensitive materials without detriment to activity via highly productive manufacturing are significant for practical uses in the field of biomedical applications. Herein, a multilayered nanofilm fabricating system is developed by inkjet printing to incorporate bFGF successfully. It is demonstrated that water mixed with glycerol as biological ink maintains stability of bFGFs through simulation and experimental study. With highly stable bFGFs, the proliferation of human dermal fibroblast is enhanced and the undifferentiated state of induced pluripotent stem cell is maintained by the controlled release of bFGF. Nanofilm incorporating basic fibroblast growth factors (bFGFs)are fabricated using inkjet printing and layer‐by‐layer assembly. During fabrication process, activity of bFGFs is highly stabilized by mixture of glycerol and water (3:7). The bFGFs released from nanofilm have an effect on a various kinds of cells, such as proliferation of human dermal fibroblast or differentiation of induced pluripotent stem cell.