The Substructure of the Endothelial Glycocalyx in Rat Aorta and Its Interaction with the Low-Density Lipoproteins.

The influx and retention of the low-density lipoproteins (LDLs) in the subendothelial space are one of the early events of atherosclerosis. Initially, LDLs must traverse the endothelial glycocalyx, which is increasingly recognized for its critical role in preventing LDL penetration. However, the precise substructure of the glycocalyx and its working mechanism are still unknown.

Bioinspired Lipid Nanoparticles with Prolonged Cartilage Retention Boost Regeneration in Early Osteoarthritis and Large Cartilage Defects.

Osteoarthritis (OA) leads to the progressive degeneration of articular cartilage, yet there is currently no effective treatment available for both the early and late stages of osteoarthritis. Cartilage regeneration requires the action and prolonged retention of multiple drugs at injured sites to recruit endogenous cells and facilitate cartilage formation. Here, we propose a cartilage-binding-peptide-modified lipid nanoparticle as a drug carrier to achieve sustained release of protein (TGF-β3) and small molecular drugs (KGN) for one month.

Palmitoylation of PD-L1 Regulates Its Membrane Orientation and Immune Evasion.

Recently identified palmitoylation of PD-L1 is essential for immune regulation. To elucidate the underlying molecular mechanism, we performed giant plasma membrane vesicle (GPMV) experiments, μs-scale all-atom molecular dynamics (MD) simulations, fluorescence resonance energy transfer (FRET) experiments, and immune killing experiments. GPMV experiments indicated that PD-L1 palmitoylation enhanced its lipid raft affinity.

Annealing synchronizes the TOM complex with Tom7 in a new orientation.

Annealing is an ideal approach to synchronizing soluble proteins into their minimum-energy states via tandem heating and cooling treatments. Like soluble proteins, many membrane proteins also suffer intrinsic structural flexibility, the major obstacle to high-resolution structural determination. How to apply annealing onto membrane proteins remains unexplored.

Regulate PD-L1's membrane orientation thermodynamics with hydrophobic nanoparticles.

Tumor cells can escape from immune killing by binding their programmed death ligand-1 (PD-L1) to the programmed cell death protein 1 (PD-1) of T cells. These immune checkpoint proteins (PD-L1/PD-1) have become very important drug targets, since blocking PD-L1 or PD-1 can recover the killing capability of T cells against tumor cells. Instead of targeting the binding interface between PD-L1 and PD-1, we explored the possibility of regulating the membrane orientation thermodynamics of PD-L1 with ligand-modified ultra-small hydrophobic nanoparticles (NPs) using μs-scale coarse-grained molecular dynamics (MD) simulations in this work.

CHARMM36 All-Atom Gas Model for Lipid Nanobubble Simulation.

Lipid nanobubbles with different gas cores may integrate the biocompatibility of lipids, powerful physicochemical properties of nanobubbles, and therapeutic effects of gas molecules, which thus promote enormous biomedical applications such as ultrasound molecular imaging, gene/drug delivery, and gas therapy. In order for further more precise applications, the exact molecular mechanisms for the interactions between lipid nanobubbles and biological systems should be studied. Molecular dynamics (MD) simulation provides a powerful computational tool for this purpose.

A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion.

Cargo translocation across membranes is a crucial aspect of secretion. In conventional secretion signal peptide-equipped proteins enter the endoplasmic reticulum (ER), whereas a subset of cargo lacking signal peptides translocate into the ER-Golgi intermediate compartment (ERGIC) in a process called unconventional protein secretion (UcPS). The regulatory events at the ERGIC in UcPS are unclear.

Neuroinflammation catching nanobubbles for microglia-neuron unit modulation against epilepsy.

Epilepsy is a common neurological disease caused by synchronous firing of hyperexcitable neurons. Currently, patients with epilepsy are typically treated with antiseizure medicines that work by interrupting the hyperexcitability or hypersynchrony of localized neurons or by inhibiting excitatory neurotransmission. However, these drugs do not treat the underlying causes of epilepsy, and nearly one-third of patients have seizures that cannot be controlled by these medications.

Membrane Domain Anti-Registration Induces an Intrinsic Transmembrane Potential.

Plasma membrane segregation into various nanoscale membrane domains is driven by distinct interactions between diverse lipids and proteins. Among them, liquid-ordered () membrane domains are defined as "lipid rafts" and liquid-disordered () ones as "lipid non-rafts". Using model membrane systems, both intra-leaflet and inter-leaflet dynamics of these membrane domains are widely studied.

Bio-inspired peptide-conjugated liposomes for enhanced planktonic bacteria killing and biofilm eradication.

Developing new antimicrobial agents has become an urgent task to address the increasing prevalence of multidrug-resistant pathogens and the emergence of biofilms. Cationic antimicrobial peptides (AMPs) have been regarded as promising candidates due to their unique non-specific membrane rupture mechanism. However, a series of problems with the peptides hindered their practical application due to their high toxicity and low bioactivity and stability.

The stiffness-dependent tumor cell internalization of liquid metal nanoparticles.

The properties of nanoparticle (NP) carriers, such as size, shape and surface state, have been proven to dramatically affect their uptake by tumor cells, thereby influencing and determining the effect of nanomedicine on tumor theranostics. However, the effect of the stiffness of NPs on their cellular internalization remains unclear, especially for circumstances involving active or passive NP targeting. In this work, we constructed eutectic gallium indium liquid metal NPs with the same particle size, shape and surface charge properties but distinct stiffness tailoring the surface oxidation and silica coating.

Molecular dynamics simulation insights into the cellular uptake of elastic nanoparticles through human pulmonary surfactant.

The interaction between inhaled nanoparticles (NPs) and the pulmonary surfactant (PS) monolayer has drawn significant attention due to its potential in drug delivery design and application for respiratory therapeutics in active and passive cellular uptake pathways. Even though much attention has been given to explore the interaction between NPs and the PS monolayer, the effects of the NP elasticity on the translocation across the PS monolayer have not been thoroughly studied. Here, we performed a series of coarse-grained (CG) molecular dynamics simulations to study active or passive cellular uptake pathways of three NPs with different elasticities through a PS monolayer.

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane.

Docosahexaenoic acid (DHA) is a ω-3 polyunsaturated fatty acid, which can be uptaken by cells and is essential for proper neuronal and retinal function. However, the detailed physical impact of DHA molecules on the plasma membrane is still unclear. Hence, in this work, we carried out μs-scale coarse-grained molecular dynamics (MD) simulations to reveal the interactions between DHA molecules and a model cell membrane.

Evaluation of Interactions between SARS-CoV-2 RBD and Full-Length ACE2 with Coarse-Grained Molecular Dynamics Simulations.

Compared to all-atom models, coarse-grained models enable the investigation of the dynamics of simulation systems on a much larger length scale and a longer time scale, which makes them suitable for studying macromolecular systems. Hence, in this work, we performed multiple μs-scale Martini coarse-grained molecular dynamics simulations to reveal the interaction details between SARS-CoV-2 RBD and full-length human ACE2. Besides, the key coarse-grained systems were backmapped into the corresponding all-atom system for the display of structural details.

Ultra-Stretchable and Fast Self-Healing Ionic Hydrogel in Cryogenic Environments for Artificial Nerve Fiber.

Self-healing materials behave with irreplaceable advantages in biomimetic intelligent robots (BIR) for avoiding or reducing safety hazards and economic losses from accidental damage during service. However, the self-healing ability is unreservedly lost and even becomes rigid and fragile in the cryogenic environment where BIR are precisely needed. Here, the authors report a versatile ionic hydrogel with fast self-healing ability, ultra-stretchability, and stable conductivity, even at -80 °C.

Designing amphiphilic Janus nanoparticles with tunable lipid raft affinity molecular dynamics simulation.

Due to the differential interactions among lipids and proteins, the plasma membrane can segregate into a series of functional nanoscale membrane domains ("lipid rafts"), which are essential in multiple biological processes such as signaling transduction, protein trafficking and endocytosis. On the other hand, Janus nanoparticles (NPs) have shown great promise in various biomedical applications due to their asymmetric characteristics and can integrate different surface properties and thus synergetic functions. Hence, in this work, we aim to design an amphiphilic Janus NP to target and regulate lipid rafts tuning its surface ligand amphiphilicity using coarse-grained molecular dynamics (MD) simulations.

Surface ligand rigidity modulates lipid raft affinity of ultra-small hydrophobic nanoparticles: insights from molecular dynamics simulations.

Differential preferences between lipids and proteins drive the formation of dynamical nanoscale membrane domains (lipid rafts), which play key roles in the proper functioning of cells. On the other hand, due to the potent physicochemical properties of nanoparticles (NPs), they have been widely used in drug delivery, bio-imaging and regulating various essential biological processes of the cells. Hence, in this work, we aim to design ultra-small hydrophobic NPs with tunable raft affinity, which is supposed to partition into the hydrophobic region of lipid membranes and be able to regulate the dynamics of the lipid raft domains.

Cell membrane-biomimetic coating via click-mediated liposome fusion for mitigating the foreign-body reaction.

The foreign-body reaction (FBR) caused by the implantation of synthetic polymer scaffolds seriously affects tissue-biomaterial integration and tissue repair. To address this issue, we developed a cell membrane-biomimetic coating formed by "click"-mediated liposome immobilization and fusion on the surface of electrospun fibers to mitigate the FBR. Utilization of electrospun polystyrene microfibrous scaffold as a model matrix, we deposited azide-incorporated silk fibroin on the surface of the fibers by the layer-by-layer assembly, finally, covalently modified with clickable liposomes via copper-free SPAAC click reaction.

Transmembrane potential of physiologically relevant model membranes: Effects of membrane asymmetry.

Transmembrane potential difference (V) plays important roles in regulating various biological processes. At the macro level, V can be experimentally measured or calculated using the Nernst or Goldman-Hodgkin-Katz equation. However, the atomic details responsible for its generation and impact on protein and lipid dynamics still need to be further elucidated.

Correction: Optimization of hydrophobic nanoparticles to better target lipid rafts with molecular dynamics simulations.

Correction for 'Optimization of hydrophobic nanoparticles to better target lipid rafts with molecular dynamics simulations' by Xiaoqian Lin et al., Nanoscale, 2020, 12, 4101-4109, DOI: 10.1039/C9NR09226A.

Single-Molecule Study of Peptides with the Same Amino Acid Composition but Different Sequences by Using an Aerolysin Nanopore.

Nanopores are original sensors employed for highly sensitive peptides/proteins detection. Herein, we describe the use of an aerolysin nanopore to identify two similar model peptides, YEQYEQQDDDRQQQ (YEQ2Q3) and QDDDRQQQYEQYEQ (Q3YEQ2), with the same amino acid composition but different sequences. All-atom molecular dynamics (MD) simulations reveal that YEQ2Q3 possesses fewer hydrogen bonds and a more extended conformation than Q3YEQ2.

A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion.

Many cytosolic proteins lacking a signal peptide, called leaderless cargoes, are secreted through unconventional secretion. Vesicle trafficking is a major pathway involved. It is unclear how leaderless cargoes enter into the vesicle.

A Review on Applications of Computational Methods in Drug Screening and Design.

Drug development is one of the most significant processes in the pharmaceutical industry. Various computational methods have dramatically reduced the time and cost of drug discovery. In this review, we firstly discussed roles of multiscale biomolecular simulations in identifying drug binding sites on the target macromolecule and elucidating drug action mechanisms.