7 research outputs found
Interplay between Nanoparticle Wrapping and Clustering of Inner Anchored Membrane Proteins
The
receptor-mediated endocytosis of nanoparticles (NPs) is known
to be size and shape dependent but regulated by membrane properties,
like tension, rigidity, and especially membrane proteins. Compared
with transmembrane receptors, which directly bind ligands coated on
NPs to provide the driving force for passive endocytosis, the hidden
role of inner anchored membrane proteins (IAMPs), however, has been
grossly neglected. Here, by applying the N-varied dissipative particle
dynamics (DPD) techniques, we present the first simulation study on
the interplay between wrapping of NPs and clustering of IAMPs. Our
results suggest that the wrapping dynamics of NPs can be regulated
by clustering of IAMPs, but in a competitive way. In the early stage,
the dispersed IAMPs rigidify the membrane and thus restrain NP wrapping
by increasing the membrane bending energy. However, once the clustering
completes, the rigidifying effect is reduced. Interestingly, the clustering
of longer IAMPs can sense NP wrapping. They are found to locate preferentially
at the boundary region of NP wrapping. More importantly, the adjacent
IAMP clustering produces a late membrane monolayer protrusion, which
finally wraps the NP from the top side. Our findings regarding the
competitive effects of IAMP clustering on NP wrapping facilitate the
molecular understanding of endocytosis and establish fundamental principles
for design of NPs for widespread biomedical applications
Ultrashort Single-Walled Carbon Nanotubes Insert into a Pulmonary Surfactant Monolayer via Self-Rotation: Poration and Mechanical Inhibition
It has been widely accepted
that longer single-walled carbon nanotubes (SWCNTs) exhibit higher
toxicity by causing severe pneumonia once inhaled, yet relatively
little is known regarding the potential toxicity of ultrashort SWCNTs,
which are of central importance to the development of suitable vehicles
for biomedical applications. Here, by combining coarse-grained molecular
dynamics (CGMD), pulling simulations, and scaling analysis, we demonstrate
that the inhalation toxicity of ultrashort SWCNTs (1.5 nm < <i>l</i> < 5.5 nm) can be derived from the unique behaviors
on interaction with the pulmonary surfactant monolayer (PSM), which
is located at the air–water interface of alveoli and forms
the frontline of the lung host defense. Molecular dynamics (MD) simulations
suggest that ultrashort SWCNTs spontaneously insert into the PSM via
fast self-rotation. Further translocation toward the water or air
phase involves overcoming a high free-energy barrier, indicating that
removal of inhaled ultrashort SWCNTs from the PSM is difficult, possibly
leading to the accumulation of SWCNTs in the PSM, with prolonged retention
and increased inflammation potentials. Under certain conditions, the
inserted SWCNTs are found to open hydrophilic pores in the PSM via
a mechanism that mimics that of the antimicrobial peptide. Besides,
the mechanical property of the PSM is inhibited by the deposited ultrashort
SWCNTs through segregation of the inner lipid molecules from the outer
phase. Our results bring to the forefront
the concern of the inhalation toxicity of ultrashort SWCNTs and provide
guidelines for future design of inhaled nanodrug carriers with minimized
side effects
Development of ProPhenol/Ti(IV) Catalyst for Asymmetric Hydroxylative Dearomatization of Naphthols
By development of ProPhenol/Ti(IV) catalysts, a catalytic
enantioselective
hydroxylative dearomatization of naphthols is achieved by using TBHP
as a simple oxidative reagent. The side coordinative chain equipped
on the C1-position of β-naphthols plays an important role for
initiating this asymmetric hydroxylative reaction, which might be
a result of the proper cocoordination effects to the titanium center
in the catalyst. A reasonable catalytic cycle is proposed, the catalytic
system is applied to a reasonable range of this type of phenolic compound,
and related concise transformations are carried out
Role of Lipid Coating in the Transport of Nanodroplets across the Pulmonary Surfactant Layer Revealed by Molecular Dynamics Simulations
Hydrophilic drugs can be delivered into lungs via nebulization
for both local and systemic therapies. Once inhaled, ultrafine nanodroplets
preferentially deposit in the alveolar region, where they first interact
with the pulmonary surfactant (PS) layer, with nature of the interaction
determining both efficiency of the pulmonary drug delivery and extent
of the PS perturbation. Here, we demonstrate by molecular dynamics
simulations the transport of nanodroplets across the PS layer being
improved by lipid coating. In the absence of lipids, bare nanodroplets
deposit at the PS layer to release drugs that can be directly translocated
across the PS layer. The translocation is quicker under higher surface
tensions but at the cost of opening pores that disrupt the ultrastructure
of the PS layer. When the PS layer is compressed to lower surface
tensions, the nanodroplet prompts collapse of the PS layer to induce
severe PS perturbation. By coating the nanodroplet with lipids, the
disturbance of the nanodroplet on the PS layer can be reduced. Moreover,
the lipid-coated nanodroplet can be readily wrapped by the PS layer
to form vesicular structures, which are expected to fuse with the
cell membrane to release drugs into secondary organs. Properties of
drug bioavailability, controlled drug release, and enzymatic tolerance
in real systems could be improved by lipid coating on nanodroplets.
Our results provide useful guidelines for the molecular design of
nanodroplets as carriers for the pulmonary drug delivery
Role of Lipid Coating in the Transport of Nanodroplets across the Pulmonary Surfactant Layer Revealed by Molecular Dynamics Simulations
Hydrophilic drugs can be delivered into lungs via nebulization
for both local and systemic therapies. Once inhaled, ultrafine nanodroplets
preferentially deposit in the alveolar region, where they first interact
with the pulmonary surfactant (PS) layer, with nature of the interaction
determining both efficiency of the pulmonary drug delivery and extent
of the PS perturbation. Here, we demonstrate by molecular dynamics
simulations the transport of nanodroplets across the PS layer being
improved by lipid coating. In the absence of lipids, bare nanodroplets
deposit at the PS layer to release drugs that can be directly translocated
across the PS layer. The translocation is quicker under higher surface
tensions but at the cost of opening pores that disrupt the ultrastructure
of the PS layer. When the PS layer is compressed to lower surface
tensions, the nanodroplet prompts collapse of the PS layer to induce
severe PS perturbation. By coating the nanodroplet with lipids, the
disturbance of the nanodroplet on the PS layer can be reduced. Moreover,
the lipid-coated nanodroplet can be readily wrapped by the PS layer
to form vesicular structures, which are expected to fuse with the
cell membrane to release drugs into secondary organs. Properties of
drug bioavailability, controlled drug release, and enzymatic tolerance
in real systems could be improved by lipid coating on nanodroplets.
Our results provide useful guidelines for the molecular design of
nanodroplets as carriers for the pulmonary drug delivery
Role of Lipid Coating in the Transport of Nanodroplets across the Pulmonary Surfactant Layer Revealed by Molecular Dynamics Simulations
Hydrophilic drugs can be delivered into lungs via nebulization
for both local and systemic therapies. Once inhaled, ultrafine nanodroplets
preferentially deposit in the alveolar region, where they first interact
with the pulmonary surfactant (PS) layer, with nature of the interaction
determining both efficiency of the pulmonary drug delivery and extent
of the PS perturbation. Here, we demonstrate by molecular dynamics
simulations the transport of nanodroplets across the PS layer being
improved by lipid coating. In the absence of lipids, bare nanodroplets
deposit at the PS layer to release drugs that can be directly translocated
across the PS layer. The translocation is quicker under higher surface
tensions but at the cost of opening pores that disrupt the ultrastructure
of the PS layer. When the PS layer is compressed to lower surface
tensions, the nanodroplet prompts collapse of the PS layer to induce
severe PS perturbation. By coating the nanodroplet with lipids, the
disturbance of the nanodroplet on the PS layer can be reduced. Moreover,
the lipid-coated nanodroplet can be readily wrapped by the PS layer
to form vesicular structures, which are expected to fuse with the
cell membrane to release drugs into secondary organs. Properties of
drug bioavailability, controlled drug release, and enzymatic tolerance
in real systems could be improved by lipid coating on nanodroplets.
Our results provide useful guidelines for the molecular design of
nanodroplets as carriers for the pulmonary drug delivery
Role of Lipid Coating in the Transport of Nanodroplets across the Pulmonary Surfactant Layer Revealed by Molecular Dynamics Simulations
Hydrophilic drugs can be delivered into lungs via nebulization
for both local and systemic therapies. Once inhaled, ultrafine nanodroplets
preferentially deposit in the alveolar region, where they first interact
with the pulmonary surfactant (PS) layer, with nature of the interaction
determining both efficiency of the pulmonary drug delivery and extent
of the PS perturbation. Here, we demonstrate by molecular dynamics
simulations the transport of nanodroplets across the PS layer being
improved by lipid coating. In the absence of lipids, bare nanodroplets
deposit at the PS layer to release drugs that can be directly translocated
across the PS layer. The translocation is quicker under higher surface
tensions but at the cost of opening pores that disrupt the ultrastructure
of the PS layer. When the PS layer is compressed to lower surface
tensions, the nanodroplet prompts collapse of the PS layer to induce
severe PS perturbation. By coating the nanodroplet with lipids, the
disturbance of the nanodroplet on the PS layer can be reduced. Moreover,
the lipid-coated nanodroplet can be readily wrapped by the PS layer
to form vesicular structures, which are expected to fuse with the
cell membrane to release drugs into secondary organs. Properties of
drug bioavailability, controlled drug release, and enzymatic tolerance
in real systems could be improved by lipid coating on nanodroplets.
Our results provide useful guidelines for the molecular design of
nanodroplets as carriers for the pulmonary drug delivery