Machine Learning-Assisted Design of Thin-Film Composite Membranes for Solvent Recovery.

Organic solvents are extensively utilized in industries as raw materials, reaction media, and cleaning agents. It is crucial to efficiently recover solvents for environmental protection and sustainable manufacturing. Recently, organic solvent nanofiltration (OSN) has emerged as an energy-efficient membrane technology for solvent recovery; however, current OSN membranes are largely fabricated by trial-and-error methods. In this study, for the first time, we develop a machine learning (ML) approach to design new thin-film composite membranes for solvent recovery. The monomers used in interfacial polymerization, along with membrane, solvent and solute properties, are featurized to train ML models via gradient boosting regression. The ML models demonstrate high accuracy in predicting OSN performance including solvent permeance and solute rejection. Subsequently, 167 new membranes are designed from 40 monomers and their OSN performance is predicted by the ML models for common solvents (methanol, acetone, dimethylformamide, and n-hexane). New top-performing membranes are identified with methanol permeance superior to that of existing membranes. Particularly, nitrogen-containing heterocyclic monomers are found to enhance microporosity and contribute to higher permeance. Finally, one new membrane is experimentally synthesized and tested to validate the ML predictions. Based on the chemical structures of monomers, the ML approach developed here provides a bottom-up strategy toward the rational design of new membranes for high-performance solvent recovery and many other technologically important applications.

Molecular understanding of acetylcholinesterase adsorption on functionalized carbon nanotubes for enzymatic biosensors.

The immobilization of acetylcholinesterase on different nanomaterials has been widely used in the field of amperometric organophosphorus pesticide (OP) biosensors. However, the molecular adsorption mechanism of acetylcholinesterase on a nanomaterial's surface is still unclear. In this work, multiscale simulations were utilized to study the adsorption behavior of acetylcholinesterase from Torpedo californica (TcAChE) on amino-functionalized carbon nanotube (CNT) (NH2-CNT), carboxyl-functionalized CNT (COOH-CNT) and pristine CNT surfaces. The simulation results show that the active center and enzyme substrate tunnel of TcAChE are both close to and oriented toward the surface when adsorbed on the positively charged NH2-CNT, which is beneficial to the direct electron transfer (DET) and accessibility of the substrate molecule. Meanwhile, the NH2-CNT can also reduce the tunnel cost of the enzyme substrate of TcAChE, thereby further accelerating the transfer rate of the substrate from the surface or solution to the active center. However, for the cases of TcAChE adsorbed on COOH-CNT and pristine CNT, the active center and substrate tunnel are far away from the surface and face toward the solution, which is disadvantageous for the DET and transportation of enzyme substrate. These results indicate that NH2-CNT is more suitable for the immobilization of TcAChE. This work provides a better molecular understanding of the adsorption mechanism of TcAChE on functionalized CNT, and also provides theoretical guidance for the ordered immobilization of TcAChE and the design, development and improvement of TcAChE-OPs biosensors based on functionalized carbon nanomaterials.

Lysozyme Adsorption on Different Functionalized MXenes: A Multiscale Simulation Study.

Recently, MXenes, due to their abundant advantages, have been widely applied in energy storage, separation, catalysis, biosensing, et al. In this study, parallel tempering Monte Carlo and molecular dynamics methods were performed to investigate lysozyme adsorption on different functionalized Ti3C2Tx (-O, -OH, and -F). The simulation results show that lysozyme can adsorb effectively on Ti3C2Tx surfaces, and the order of interaction strength is Ti3C2O2 > Ti3C2F2 > Ti3C2(OH)2. Electrostatics together with van der Waals interactions control protein adsorption. The orientation distributions of lysozyme adsorbed on the Ti3C2O2 and Ti3C2F2 surfaces are more concentrated than that on the Ti3C2(OH)2 surface. During adsorption, the conformation of lysozyme remains stable, suggesting the good biocompatibility of Ti3C2Tx. Besides, the distribution of the interfacial water layer on the Ti3C2Tx surface has a certain impact on protein adsorption. This study provides theoretical insights for understanding the biocompatibility of 2D Ti3C2Tx materials and may help us evaluate the engineering of their surfaces for future biorelated applications.

The interplay between surface-functionalized gold nanoparticles and negatively charged lipid vesicles.

The comprehensive understanding of the interactions between gold nanoparticles (AuNPs) and phospholipid vesicles has important implications in various biomedical applications; however, this is not yet well understood. Here, coarse-grained molecular dynamics (CGMD) simulations were performed to study the interactions between functionalized AuNPs and negatively charged lipid vesicles, and the effects of the surface chemistry and surface charge density (SCD) of AuNPs were analyzed. It is revealed that AuNPs with different surface ligands adhere to the membrane surface (anionic AuNPs) or get into the vesicle bilayer (hydrophobic and cationic AuNPs). Due to the loose arrangement of lipid molecules, AuNPs penetrate curved vesicle membranes more easily than planar lipid bilayers. Cationic AuNPs present three different interaction modes with the vesicle, namely insertion, partial penetration and complete penetration, which are decided by the SCD difference. Both hydrophobic interaction and electrostatic interaction play crucial roles in the interplay between cationic AuNPs and lipid vesicles. For the cationic AuNP with a low SCD, it gets into the lipid bilayer without membrane damage through the hydrophobic interaction, and it is finally stabilized in the hydrophobic interior of the vesicle membrane in a thermodynamically stable "snorkeling" configuration. For the cationic AuNP with a high SCD, it crosses the vesicle membrane and gets into the vesicle core through a membrane pore induced by strong electrostatic interaction. In this process, the membrane structure is destroyed. These findings provide a molecular-level understanding of the interplay between AuNPs and lipid vesicles, which may further expand the application of functional AuNPs in modern biomedicine.

Lysozyme Adsorption on Porous Organic Cages: A Molecular Simulation Study.

Recently, porous organic cages (POCs) have emerged as a novel porous material with many merits and are widely utilized in many application fields. In this work, for the first time, molecular dynamics simulations were performed to investigate the mechanism of lysozyme adsorption onto the CC3 crystal, a kind of widely studied POC material. The simulation results show that lysozyme adsorbs onto the surface of CC3 with "top end-on," "back-on," or "side-on" orientations. It is found that the van der Waals interaction is the primary contribution to the binding; the conformation of the lysozyme is well preserved during the adsorption process. This provides some evidence for its biocompatibility and feasibility in biorelated applications. Arginine plays an important role in mediating the adsorption through nonpolar aliphatic chains. More importantly, the distribution and structure of the water layer on the POC surface has a significant impact on adsorption. This study provides insights into the development of POC materials with defined morphologies for the adsorption of biomolecules and may help the rational design of biorelated systems.

ACAP1 assembles into an unusual protein lattice for membrane deformation through multiple stages.

Studies on the Bin-Amphiphysin-Rvs (BAR) domain have advanced a fundamental understanding of how proteins deform membrane. We previously showed that a BAR domain in tandem with a Pleckstrin Homology (PH domain) underlies the assembly of ACAP1 (Arfgap with Coil-coil, Ankryin repeat, and PH domain I) into an unusual lattice structure that also uncovers a new paradigm for how a BAR protein deforms membrane. Here, we initially pursued computation-based refinement of the ACAP1 lattice to identify its critical protein contacts. Simulation studies then revealed how ACAP1, which dimerizes into a symmetrical structure in solution, is recruited asymmetrically to the membrane through dynamic behavior. We also pursued electron microscopy (EM)-based structural studies, which shed further insight into the dynamic nature of the ACAP1 lattice assembly. As ACAP1 is an unconventional BAR protein, our findings broaden the understanding of the mechanistic spectrum by which proteins assemble into higher-ordered structures to achieve membrane deformation.

Understanding the Cellular Uptake of pH-Responsive Zwitterionic Gold Nanoparticles: A Computer Simulation Study.

Surface functionalization of nanoparticles (NPs) with stealth polymers (e.g., hydrophilic and zwitterionic polymers) has become a common strategy to resist nonspecific protein adsorption recently. Understanding the role of surface decoration on NP-biomembrane interactions is of great significance to promote the application of NPs in biomedical fields. Herein, using coarse-grained molecular dynamics (CGMD) simulations, we investigate the interactions between stealth polymer-coated gold nanoparticles (AuNPs) and lipid membranes. The results show that AuNPs grafted with zwitterionic polymers can more easily approach the membrane surface than those coated with hydrophilic poly(ethylene glycol) (PEG), which can be explained by the weak dipole-dipole interaction between them. For zwitterionic AuNPs which can undergo pH-dependent charge conversion, different interaction modes which depend on the polymer protonation degree are found. When the protonation degree is low, the particles just adsorb on the membrane surface; at moderate protonation degrees, the particles can directly translocate across the lipid membrane through a transient hydrophilic pore formed on the membrane surface; the particles are fully wrapped by the curved lipid membrane at high protonation degrees, which may lead to endocytosis. Finally, the effect of polymer chain length on the cellular uptake of zwitterionic polymer-coated AuNPs is considered. The results demonstrate that longer polymer chain length will block the translocation of AuNPs across the lipid membrane when the protonation degree is not high; however, it can improve the transmembrane efficiency of AuNPs at high protonation degrees. We expect that these findings are of immediate interest to the design and synthesis of pH-responsive nanomaterials based on zwitterionic polymers and can prompt their further applications in the field of biomedicine.

Molecular Understanding on the Underwater Oleophobicity of Self-Assembled Monolayers: Zwitterionic versus Nonionic.

Molecular dynamics simulations are conducted to investigate the underwater oleophobicity of self-assembled monolayers (SAMs) with different head groups. Simulation results show that the order of underwater oleophobicity of SAMs is methyl < amide < oligo(ethylene glycol) (OEG) < ethanolamine (ETA) < hydroxyl < mixed-charged zwitterionic. The underwater-oil contact angles (OCAs) are <133° for all nonionic hydrophilic SAMs, while the mixed-charged zwitterionic SAMs are underwater superoleophobic (OCA can reach 180°). It appears that surfaces with stronger underwater oleophobicity have better antifouling performance. Further study on the effect of different alkyl ammonium ions on mixed-charged SAMs reveals that the underwater OCAs are >143.6° for all SAMs; mixed-charged SAMs containing primary alkyl ammonium ion are likely to possess the best underwater oleophobicity for its strong hydration capacity. It seems that alkyl sulfonate anion (SO3-) is more hydrophilic than alkyl trimethylammonium ion (NC3+) for the hydrophobic methyl groups on nitrogen atoms and that the hydration of SO3- in mixed-charged SAMs can be seriously blocked by NC3+. The monomer of SO3- should be slightly longer than that of NC3+ to obtain better underwater oleophobicity in NC3+-/SO3--SAMs. In addition, the underwater oleophobicity of SAMs might become worse at low grafting densities. This work systematically proves that a zwitterionic surface is more underwater oleophobic than a nonionic surface. These results will help for the design and development of superoleophobic surfaces.

Molecular Understanding of the Penetration of Functionalized Gold Nanoparticles into Asymmetric Membranes.

In this work, the interactions between surface-functionalized gold nanoparticles (AuNPs) and asymmetric membranes and the associated cytotoxicity were explored by coarse-grained molecular dynamics simulations. Simulation results show that the surface chemistry of AuNPs and the asymmetry of lipid membranes play significant roles. AuNPs with different signs of charges spontaneously adhere to the membrane surface or penetrate the membrane core. Also, the asymmetric distribution of charged lipids in membranes can facilitate the penetration of cationic AuNPs. Increasing the surface charge density (SCD) of AuNPs can not only improve the penetration efficiency but also lead to more disruption of the membrane structure. Moreover, the flip-flop of charged lipids in the inner leaflet can be observed during the translocation of AuNPs with a high SCD. The breakdown of membrane asymmetry may hinder the cellular internalization of AuNPs in a direct penetration mechanism. More importantly, we demonstrate that the hydrophobic contact between protruding solvent-exposed lipid tails and the hydrophobic moieties of ligands can mediate the insertion of AuNPs with a low SCD into cell membranes, which will exhibit less cytotoxicity in most in vivo applications. This may open a new exciting avenue to developing nanocarriers with a higher translocation efficiency and a lower toxicity simultaneously for biomedical applications.

Electrostatics-mediated α-chymotrypsin inhibition by functionalized single-walled carbon nanotubes.

The α-chymotrypsin (α-ChT) enzyme is extensively used for studying nanomaterial-induced enzymatic activity inhibition. A recent experimental study reported that carboxylized carbon nanotubes (CNTs) played an important role in regulating the α-ChT activity. In this study, parallel tempering Monte Carlo and molecular dynamics simulations were combined to elucidate the interactions between α-ChT and CNTs in relation to the CNT functional group density. The simulation results indicate that the adsorption and the driving force of α-ChT on different CNTs are contingent on the carboxyl density. Meanwhile, minor secondary structural changes are observed in adsorption processes. It is revealed that α-ChT interacts with pristine CNTs through hydrophobic forces and exhibits a non-competitive characteristic with the active site facing towards the solution; while it binds to carboxylized CNTs with the active pocket through a dominant electrostatic association, which causes enzymatic activity inhibition in a competitive-like mode. These findings are in line with experimental results, and well interpret the activity inhibition of α-ChT at the molecular level. Moreover, this study would shed light on the detailed mechanism of specific recognition and regulation of α-ChT by other functionalized nanomaterials.

Lipase adsorption on different nanomaterials: a multi-scale simulation study.

Candida antarctica lipase B (CalB) is an efficient biocatalyst for hydrolysis and esterification, which plays an important role in the production of biodiesel in the bioenergy industries. The ordered immobilisation of lipases on different supports would be significant for its enzymatic catalysis in some biodiesel production processes; however, the underlying mechanisms and the preferred lipase orientation are not well understood yet. In this work, a fundamental understanding of the orientation and adsorption mechanism of lipase on four different nanomaterial surfaces with different surface chemistry are explored in detail by a combination of parallel tempering Monte Carlo (PTMC) and molecular dynamics (MD) simulations. Simulation results show that lipase is strongly adsorbed onto the hydrophobic graphite surface, as reflected by the large contact area and interaction energy; while the adsorption onto the hydrophilic TiO2 surface is weak due to two strongly adhered water layers; meanwhile lipase undergoes desorption and reorientation processes. For CalB adsorption on positively and negatively charged surfaces (NH2-SAM and COOH-SAM), the orientation distributions of lipase are narrow, and opposite orientations are obtained. CalB adsorbed on NH2-SAM has its catalytic centre oriented towards the surface, which is not conducive to the substrate binding; while the catalytic centre faces toward the solution when it is adsorbed on the COOH-SAM. Besides, the native structures of CalB adsorbed on different surfaces are preserved, which indicates lipase as a robust enzyme. The simulation results will promote our understanding on how surface properties of nanomaterials, such as charge or hydrophobicity, will affect lipase immobilisation, and help us in the rational design and development of immobilised lipase carriers.

Adsorption of hydrophobin on different self-assembled monolayers: the role of the hydrophobic dipole and the electric dipole.

In this work, the adsorptions of hydrophobin (HFBI) on four different self-assembled monolayers (SAMs) (i.e., CH3-SAM, OH-SAM, COOH-SAM, and NH2-SAM) were investigated by parallel tempering Monte Carlo and molecular dynamics simulations. Simulation results indicate that the orientation of HFBI adsorbed on neutral surfaces is dominated by a hydrophobic dipole. HFBI adsorbs on the hydrophobic CH3-SAM through its hydrophobic patch and adopts a nearly vertical hydrophobic dipole relative to the surface, while it is nearly horizontal when adsorbed on the hydrophilic OH-SAM. For charged SAM surfaces, HFBI adopts a nearly vertical electric dipole relative to the surface. HFBI has the narrowest orientation distribution on the CH3-SAM, and thus can form an ordered monolayer and reverse the wettability of the surface. For HFBI adsorption on charged SAMs, the adsorption strength weakens as the surface charge density increases. Compared with those on other SAMs, a larger area of the hydrophobic patch is exposed to the solution when HFBI adsorbs on the NH2-SAM. This leads to an increase of the hydrophobicity of the surface, which is consistent with the experimental results. The binding of HFBI to the CH3-SAM is mainly through hydrophobic interactions, while it is mediated through a hydration water layer near the surface for the OH-SAM. For the charged SAM surfaces, the adsorption is mainly induced by electrostatic interactions between the charged surfaces and the oppositely charged residues. The effect of a hydrophobic dipole on protein adsorption onto hydrophobic surfaces is similar to that of an electric dipole for charged surfaces. Therefore, the hydrophobic dipole may be applied to predict the probable orientations of protein adsorbed on hydrophobic surfaces.

Simulation insights into the lipase adsorption on zeolitic imidazolate framework-8.

Zeolitic imidazolate frameworks (ZIFs) have recently emerged as immobilization matrices for biomolecules, most notably enzymes. Understanding the key factors that dominate the enzyme's catalytic activity on/in ZIFs is crucial for the development of new immobilization matrices. In this work, a combination of the parallel tempering Monte Carlo simulation and all-atom molecular dynamics simulation is performed to study the orientation and conformation of the Candida rugose lipase (CRL) adsorbed on oppositely charged and neutral ZIF-8 (i.e., ZIF-8-COOH, ZIF-8-NH2, and ZIF-8-neutral) surfaces. The results show that CRL could adsorb on all ZIF-8 surfaces, with an ordered orientation obtained on charged ZIF-8 surfaces. ZIF-8-NH2 is a good candidate for CRL immobilization since it can maximize the catalytic activity of CRL. The native conformation of CRL is well preserved on all three surfaces due to the partially water-containing surface of ZIF-8. The results could provide theoretical support for the application of porous materials in enzyme immobilization.

Porous organic cages as synthetic water channels.

Nature has protein channels (e.g., aquaporins) that preferentially transport water molecules while rejecting even the smallest hydrated ions. Aspirations to create robust synthetic counterparts have led to the development of a few one-dimensional channels. However, replicating the performance of the protein channels in these synthetic water channels remains a challenge. In addition, the dimensionality of the synthetic water channels also imposes engineering difficulties to align them in membranes. Here we show that zero-dimensional porous organic cages (POCs) with nanoscale pores can effectively reject small cations and anions while allowing fast water permeation (ca. 109 water molecules per second) on the same magnitude as that of aquaporins. Water molecules are found to preferentially flow in single-file, branched chains within the POCs. This work widens the choice of water channel morphologies for water desalination applications.

Lysozyme orientation and conformation on MoS2 surface: Insights from molecular simulations.

Two-dimensional molybdenum disulfide (MoS2) has attracted intense interest owing to its unique properties and promising biosensor applications. To develop effective biocompatible platforms, it is crucial to understand the interactions between MoS2 and biological molecules such as proteins, but little knowledge exists on the orientation and conformation of proteins on the MoS2 surface at the molecular level. In this work, the lysozyme adsorption on the MoS2 surface was studied by molecular dynamics simulations, wherein six different orientations were selected based on the different faces of lysozyme. Simulation results showed that lysozyme tends to adsorb on the MoS2 surface in an "end-on" orientation, indicating that orientations within this range are favorable for stable adsorption. The end-on orientation could be further categorized into "bottom end-on" and "top end-on" orientations. The driving forces responsible for the adsorption were dominated by van der Waals interactions and supplemented by electrostatic interactions. Further, the conformations of the lysozyme adsorbed on the MoS2 surface were basically preserved. This simulation study promotes the fundamental understanding of interactions between MoS2 and proteins and can guide the development of future biomedical applications of MoS2.

Computer simulations on the pH-sensitive tri-block copolymer containing zwitterionic sulfobetaine as a novel anti-cancer drug carrier.

In this work, dissipative particle dynamics (DPD) simulations were performed to study the self-assembled microstructures and doxorubicin (DOX) loading/release properties of pH-sensitive amphiphilic triblock copolymer: poly(ε-caprolactone)-b-poly(diethylaminoethyl methacrylate)-b-poly(sulfobetaine methacrylate) or poly (ethylene glycol methacrylate) (PCL-PDEA-PSBMA/PEGMA). Our results show that both copolymers can self-assemble into core-shell-corona micelles in aqueous environment. However, the corona structures are quite different for the two copolymer micelles. The shell layers formed by PEGMA have heterogeneous sizes while the shell layers in PCL-PDEA-PSBMA micelles are homogenous. This is mainly attributed to the stronger hydrophilicity of PSBMA than PEGMA. As the mole concentration of copolymer is increased from 10% to 50%, the microstructures formed by PCL-PDEA-PSBMA and DOX remains spherical micelles whereas PCL-PDEA-PEGMA undergoes structural transition from spherical to cylindrical and finally to lamellar micelles. Interestingly, the studied micelles have a pH-responsive drug release property, owing to the protonation of the PDEA block. The drug release process follows a "swelling-demicellization-release" mode. The multi-scale simulations demonstrate an avenue to the optimal design of nanomaterials for drug delivery with desired properties.