Effect of Nanoparticle Curvature on Its Interaction with Serum Proteins.

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm-1, respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.

Molecular Modeling of the Fluorination Effect on the Penetration of Nanoparticles across Lipid Bilayers.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

Effect of terahertz waves on the aggregation behavior of neurotransmitters.

Understanding the dynamics of neurotransmitters is crucial for unraveling synaptic transmission mechanisms in neuroscience. In this study, we investigated the impact of terahertz (THz) waves on the aggregation of four common neurotransmitters through all-atom molecular dynamics (MD) simulations. The simulations revealed enhanced nicotine (NCT) aggregation under 11.05 and 21.44 THz, with a minimal effect at 42.55 THz. Structural analysis further indicated strengthened intermolecular interactions and weakened hydration effects under specific THz stimulation. In addition, enhanced aggregation was observed at stronger field strengths, particularly at 21.44 THz. Furthermore, similar investigations on epinephrine (EPI), 5-hydroxytryptamine (5-HT), and γ-aminobutyric acid (GABA) corroborated these findings. Notably, EPI showed increased aggregation at 19.05 THz, emphasizing the influence of vibrational modes on aggregation. However, 5-HT and GABA, with charged or hydrophilic functional groups, exhibited minimal aggregation under THz stimulation. The present study sheds some light on neurotransmitter responses to THz waves, offering implications for neuroscience and interdisciplinary applications.

Unveiling the multicomponent phase separation through molecular dynamics simulation and graph theory.

Biomolecular condensates formed by multicomponent phase separation play crucial roles in diverse cellular processes. Accurate assessment of individual-molecule contributions to condensate formation and precise characterization of their spatial organization within condensates are crucial for understanding the underlying mechanism of phase separation. Using molecular dynamics simulations and graph theoretical analysis, we demonstrated quantitatively the significant roles of cation-π and π-π interactions mediated by aromatic residues and arginine in the formation of condensates in polypeptide systems. Our findings reveal temperature and chain length-dependent alterations in condensate network parameters, such as the number of condensate network layers, and changes in aggregation and connectivity. Notably, we observe a transition between assortativity and disassortativity in the condensate network. Moreover, polypeptides W, Y, F, and R consistently promote condensate formation, while the contributions of other charged and two polar polypeptides (Q and N) to condensate formation depend on temperature and chain length. Furthermore, polyadenosine and polyguanosine can establish stable connections with aromatic and R polypeptides, resulting in the reduced involvement of K, E, D, Q, and N in phase separation. Overall, this study provides a distinctive, precise, and quantitative approach to characterize the multicomponent phase separation.

Effect of maleylation and denaturation of human serum albumin on its interaction with scavenger receptors.

The specific recognition of serum proteins by scavenger receptors is critical and fundamental in many biological processes. However, the underlying mechanism of scavenger receptor-serum protein interaction remains elusive. In this work, taking scavenger receptors class A1 (SR-A1) as an example, we systematically investigate its interaction with human serum albumin (HSA) at different states through a combination of molecular docking and all-atom molecular dynamics simulations. It is found that native HSA can moderately bind to collagen-like (CL) region or scavenger receptor cysteine-rich (SRCR) region, with both electrostatic (ELE) and van der Waals (VDW) interactions, playing important roles. After maleylation, the binding energy, particularly the ELE energy, between HSA and CL region is significantly enhanced, while the binding energy between HSA and SRCR region remains nearly unchanged. Additionally, we also observe that unfolding of the secondary structures in HSA leads to a larger contact surface area between denatured HSA and CL region, but has little impact on the HSA-SRCR region interaction. Therefore, similar to maleylated HSA, denatured HSA is also more likely to bind to the CL region of SR-A1.

Duality, Hidden Symmetry, and Dynamic Isomerism in 2D Hinge Structures.

Recently, a new type of duality was reported in some deformable mechanical networks that exhibit Kramers-like degeneracy in phononic spectrum at the self-dual point. In this work, we clarify the origin of this duality and propose a design principle of 2D self-dual structures with arbitrary complexity. We find that this duality originates from the partial central inversion (PCI) symmetry of the hinge, which belongs to a more general end-fixed scaling transformation. This symmetry gives the structure an extra degree of freedom without modifying its dynamics. This results in dynamic isomers, i.e., dissimilar 2D mechanical structures, either periodic or aperiodic, having identical dynamic modes, based on which we demonstrate a new type of wave guide without reflection or loss. Moreover, the PCI symmetry allows us to design various 2D periodic isostatic networks with hinge duality. At last, by further studying a 2D nonmechanical magnonic system, we show that the duality and the associated hidden symmetry should exist in a broad range of Hamiltonian systems.

Effect of the Graphene Nanosheet on Functions of the Spike Protein in Open and Closed States: Comparison between SARS-CoV-2 Wild Type and the Omicron Variant.

The spread of coronavirus disease 2019 caused by SARS-CoV-2 and its variants has become a global health crisis. Although there were many attempts to use nanomaterials-based devices to fight against SARS-CoV-2, it still remains elusive as to how the nanomaterials interact with SARS-CoV-2 and affect its biofunctions. Here, taking the graphene nanosheet (GN) as the model nanomaterial, we investigate its interaction with the spike protein in both WT and Omicron by molecular simulations. In the closed state, the GN can insert into the region between the receptor binding domain (RBD) and the N-terminal domain (NTD) in both wild type (WT) and Omicron, which keeps the RBD in the down conformation. In the open state, the GN can hamper the binding of up RBD to ACE2 in WT, but it has little impact on up RBD and, even worse, stimulates the down-to-up transition of down RBDs in Omicron. Moreover, the GN can insert in the vicinity of the fusion peptide in both WT and Omicron and prevents the detachment of S1 from the whole spike protein. The present study reveals the effect of the SARS-CoV-2 variant on the nanomaterial-spike protein interaction, which informs prospective efforts to design functional nanomaterials against SARS-CoV-2.

Efficient calculation of protein-ligand binding free energy using GFN methods: the power of the cluster model.

Protein-ligand interactions are crucial in many biochemical processes and biomedical applications, yet accurately calculating the binding free energy of the interactions still remains challenging. In this work, we systematically investigate the performance of a generic force field GFN-FF and some semi-empirical quantum mechanical (SQM) methods (GFNn, n = 0, 1, 2) in terms of the accuracy of the calculated binding free energy. It is found that the performance of the GFN-FF method is quite good in a neutral-ligand system since the Pearson correlation coefficient (rp) is 0.70 and the mean absolute error (MAE) is 5.49 kcal mol-1. However, it may fail in a charged-ligand system (the MAE is 18.98 kcal mol-1). Moreover, we also propose a cluster model (i.e., truncating the protein at a given cutoff) along with the SQM method in the GFN family. Importantly, the GFN2-xTB shows the best performance among the SQM methods (the MAE is 4.91 kcal mol-1 and 10.25 kcal mol-1 in the neutral-ligand and charged-ligand systems, respectively), much better than GFN-FF in the charged-ligand system. Notably, the computing cost of the GFN2-xTB in the appropriate cluster model is even lower than that of the GFN-FF (in the entire complex). The present study sheds some light on the potential power of the GFN family in the efficient calculation of the binding free energy in bio-systems.

Breakdown of Ergodicity and Self-Averaging in Polar Flocks with Quenched Disorder.

We show that spatial quenched disorder affects polar active matter in ways more complex and far reaching than heretofore believed. Using simulations of the 2D Vicsek model subjected to random couplings or a disordered scattering field, we find in particular that ergodicity is lost in the ordered phase, the nature of which we show to depend qualitatively on the type of quenched disorder: for random couplings, it remains long-range ordered, but qualitatively different from the pure (disorderless) case. For random scatterers, polar order varies with system size but we find strong non-self-averaging, with sample-to-sample fluctuations dominating asymptotically, which prevents us from elucidating the asymptotic status of order.

Self-Assembly of Isostatic Self-Dual Colloidal Crystals.

Self-dual structures whose dual counterparts are themselves possess unique hidden symmetry, beyond the description of classical spatial symmetry groups. Here we propose a strategy based on a nematic monolayer of attractive half-cylindrical colloids to self-assemble these exotic structures. This system can be seen as a 2D system of semidisks. By using Monte Carlo simulations, we discover two isostatic self-dual crystals, i.e., an unreported crystal with pmg space-group symmetry and the twisted kagome crystal. For the pmg crystal approaching the critical point, we find the double degeneracy of the full phononic spectrum at the self-dual point and the merging of two tilted Weyl nodes into one critically tilted Dirac node. The latter is "accidentally" located on the high-symmetry line. The formation of this unconventional Dirac node is due to the emergence of the critical flatbands at the self-dual point, which are linear combinations of "finite-frequency" floppy modes. These modes can be understood as mechanically coupled self-dual rhombus chains vibrating in some unique uncoupled ways. Our work paves the way for designing and fabricating self-dual materials with exotic mechanical or phononic properties.

Improving the Performance of MM/PBSA in Protein-Protein Interactions via the Screening Electrostatic Energy.

Accurate calculation of protein-protein binding free energy is of great importance in biological and medical science, yet it remains a hugely challenging problem. In this work, we develop a new strategy in which a screened electrostatic energy (i.e., adding an exponential damping factor to the Coulombic interaction energy) is used within the framework of the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Our results show that the Pearson correlation coefficient in the modified MM/PBSA is over 0.70, which is much better than that in the standard MM/PBSA, especially in the Amber14SB force field. In particular, the performance of the standard MM/PBSA is very poor in a system where the proteins carry like charges. Moreover, we also calculated the mean absolute error (MAE) between the calculated and experimental ΔG values and found that the MAE in the modified MM/PBSA was indeed much smaller than that in the standard MM/PBSA. Furthermore, the effect of the dielectric constant of the proteins and the salt conditions on the results was also investigated. The present study highlights the potential power of the modified MM/PBSA for accurately predicting the binding energy in highly charged biosystems.

Self-Assembled Binary Photonic Crystals under the Active Confinement and Their Light Trapping.

The self-assembly of oppositely charged colloidal ellipsoids and spheres under active confinement is first proposed to achieve long-range ordered photonic crystals. Compared with the conventional passive confinement, a characteristic of the active confinement is that boundaries are movable. Our Brownian dynamics simulations show that dynamic steady structures, similar to quasi-2D colloidal crystals, can be obtained under the strong confinement when the two boundaries periodically oscillate together. The in-plane structures can be regulated by changing the charge ratio of the two kinds of particles. These dynamic steady structures are determined by the minimum electrostatic energy with the aid of increased mobility of confined particles, which are not available in equilibrium. Numerical simulations verify that light can be perfectly confined in this dielectric binary photonic slab without any radiation, which corresponds to a typical optical bound state with divergent lifetime and ultrasharp spectral profile. Given the changeable geometry of this photonic slab, the trapped optical field might be applicable to enhanced light-matter interactions. In addition, for thicker layers, layer-by-layer ordered structures occur spontaneously, driven by the active confinement, while no global order occurs in the passive confinement. Our results show that the boundary motion can become an important factor affecting self-assembled structure and function.

On-Surface Cascade Reaction Based on Successive Debromination via Metal-Organic Coordination Template.

Precise control over on-surface covalent reaction pathways is crucial for engineering organic nanostructures with the single-atom precision. Herein, we demonstrate a step-by-step control of an on-surface cascade covalent reaction based on a successive debromination templated by noncovalent metal-organic coordination motifs. The molecular precursor is predesigned with different reactive sites and functional ligands, allowing for both chemical and structural tuning during on-surface reactions. Through the Fe-terpyridine template effect, we are able to direct the reaction to proceed in a three-step cascade pathway and finally to achieve a porous polyarylene nanoribbon structure. The approach opens new opportunities for construction of on-surface organic nanostructures in a predictable manner.

Controlling the Interaction of Nanoparticles with Cell Membranes by the Polymeric Tether.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.

Globule-stretch transition of a self-attracting chain in the repulsive active particle bath.

Folding and unfolding of a chain structure are often manipulated in experiments by tuning the pH, temperature, single-molecule forces or shear fields. Here, we carry out Brownian dynamics simulations to explore the behavior of a single self-attracting chain in a suspension of self-propelling particles (SPPs). As the propelling force increases, the globule-stretch (G-S) transition of the chain occurs due to the enhanced disturbance from the SPPs. Two distinct mechanisms of the transition in the limits of low and high rotational diffusion rates of SPPs have been observed: shear-induced stretching at a low rate and collision-induced melting at a high rate. The G-S and S-G (stretch-globule) curves form a hysteresis loop at the low rate, while they merge at the high rate. Besides, we find that two competing effects result in a non-monotonic dependence of the G-S transition on SPP density at the low rate. Our results suggest an alternative approach to manipulating the folding and unfolding of (bio)polymers by utilizing active agents.

Computational Design of a Functionalized Substrate for Capturing Nanoparticles with Specific Size and Shape.

The efficient capture of nanoscopic particulates plays a key role in many scientific fields like filtration and fabrication of nanocomposites as well as biosensors. In this work, we design two types of nanosubstrates to capture the nanoparticle with specific property by using Brownian dynamics simulations. It is found that the substrate coated with copolymers (composed of nonspecific block and specific block) can be used to capture the nanoparticle with different sizes but its capture efficiency of nanoparticles with different shapes is very low. To overcome such problem, the other substrate containing shaped holes is also designed. By conducting a serial of control simulations, we find that the nonspecific polymers at the bottom and on the rim of the hole have great impact on the sensitive capture. The present study may provide some physical insights into the experimental design of nanodevices in real applications.

Counteranion Modulated Crystal Growth and Function of One-Dimensional Homochiral Coordination Polymers: Morphology, Structures, and Magnetic Properties.

Four pairs of enantiomeric dysprosium(III) phosphonates, namely, R- or S-[Dy3(pempH2)2(pempH)7]2(NO3)4·12H2O ( R-1 or S-1), R- or S-[Dy3(pempH)7(pempH2)2]Cl2·2H2O ( R-2 or S-2), R- or S-[Dy3(pempH)7(pempH2)2]Br2·2H2O ( R-3 or S-3), and R- or S-[Dy11(pempH2)6(pempH)27](CF3SO3)6·22H2O ( R-4 or S-4) are reported, where R- or S-pempH2 represent R- or S-(1-phenylethyl)amino] methylphosphonic acid. All show homochiral chain structures, charge-balanced by counteranions. A comparison of the crystal morphologies of the R-isomers reveals that the overall shapes are quite similar for the four compounds, but the aspect ratio changes remarkably following the sequence: R-1 < R-2 < R-3 < R-4. The sequence is in agreement with the decreasing interchain interactions related to different counteranions, which is rationalized by molecular simulations. The counteranions also influence the intrachain structures and the local coordination environments of the DyIII ions. As a result, compounds R-2 and R-3 exhibit distinct dual relaxation processes at zero dc field with the effective energy barriers for the slow- and fast-relaxation being 79.1 and 37.6 K for R-2, and 80.0 and 39.1 K for R-3, respectively. For compounds R-1 and R-4, however, slow magnetic relaxation is also observed at zero dc field but without the appearance of maxima down to 1.8 K.

Computational investigation on DNA sequencing using functionalized graphene nanopores.

Fast, low-cost and reliable DNA sequencing is one of the most desirable innovations in recent years, which can pave the way for high throughput, label-free and inexpensive personalized genome sequencing techniques. Although graphene-based nanopore devices hold great promise for next-generation DNA sequencing, it is still a challenging problem to detect different DNA sequences efficiently and accurately. In the present work, the translocation of four homogeneous DNA strands (i.e., poly(A)20, poly(C)20, poly(G)20, and poly(T)20) through the functionalized graphene nanopores is investigated by all-atom molecular dynamic simulations. Interestingly, it is found that the four types of bases could be identified by different ionic currents when they pass through the hydrogenated and hydroxylated pores. For the hydrogenated nanopore, the difference in the ionic current for the four bases is mainly attributed to the different electrostatic interactions between the base and the ion. For the hydroxylated nanopore, apart from the electrostatic interactions, the position of a nucleotide inside the nanopore and the dwell time of an ion around the nucleotide also play an important role in the ionic current. The present study could be helpful to better design a novel device for DNA sequencing in the future.

Microrotor of a chain-grafted colloidal disk immersed in the active bath: The impact of particle concentration, grafting density, and chain rigidity.

In an earlier work, we discussed the possibility to realize a microrotor by immersing a chain-grafted colloidal disk in a thin film of active-particle suspension. Under certain conditions, the colloidal disk rotates unidirectionally driven by the bath active particles. Here we systematically study the role of active-particle concentration, grafting density, and chain rigidity in the phenomenon of the spontaneous symmetry breaking of the chain configurations and the unidirectional rotation of the disk. We find that high chain rigidity can help stabilize both the collective asymmetric chain configurations and the rotation of the disk, while it has a weak impact on the rotational speed/efficiency. Increasing the number of grafted chains can also stabilize the rotation but has a negative impact on the rotational speed/efficiency. Active particles power the rotation of the colloidal disk, yet their contribution saturates beyond a certain concentration. Our work provides new insights into the active systems with chain-structured objects and the design of soft/deformable micromachines.

Self-Assembly and Local Manipulation of Au-Pyridyl Coordination Networks on Metal Surfaces.

Using scanning tunnelling microscopy (STM), we demonstrate that Au-pyridyl coordination can be used to assemble two-dimensional coordination network structures on metal surfaces. The polymorphism of the coordination network structures can be manipulated at both the micro- and nanoscale. Using the same organic ligand, we assembled two distinct polymorphic network structures, which were assisted by threefold Au-pyridyl coordination on Ag(111) with predeposited Au atoms (α-network), and by twofold Au-pyridyl coordination on Au(111) (ß-network), respectively. Specifically on the Au(111) surface, single-oriented ß-network domains as large as ≈400 nm were selected by thermal annealing. We ascribe this global control strategy to distinct Au bonding modes tuned by molecule-substrate interactions. Using an STM tip, we succeeded in creating α-network domains (≈10 nm) locally within the homogeneous ß-network domain areas on Au(111) in a controlled manner.