Falin Tian

Internalization pathways of nanoparticles and their interaction with a vesicle

In this work we perform large scale dissipative particle dynamics (DPD) simulations to study the interaction between nanoparticles (NPs) and vesicles, and discuss their potential implications for NP–cell interactions. First, we determine the different pathways of NP internalization and their dependence on NP size, NP concentration, vesicle excess area, and NP–vesicle attraction. In particular, we identify three pathways for spontaneous NP penetration, which are here called the cooperative chain-like penetration, direct penetration and inverted micelle-like penetration, and investigate how different factors affect the penetration processes. Then, we demonstrate that adsorption of NPs often induces NP clustering on the outer and/or inner surfaces of vesicles, leading to different vesicle responses, including the change of vesicle morphology, formation of protuberance, and vesicle rupture.

Curvature modulates the self-assembly of amphiphilic molecules

In this work, we used lattice Monte Carlo simulations and theoretical model calculations to show how the self-assembly of adsorbed amphiphilic molecules is affected by the local curvature of solid surfaces. It is found that, beyond a critical curvature value, solid surface geometry governs the spatial ordering of aggregates and may induce the morphological transitions. The simulation results show how the curvature of solid surfaces modulates the distribution of aggregates: the anisotropy in local curvature along and perpendicular to the cylindrical surfaces tends to generate orientationally ordered cylindrical micelles. To account for the morphological transitions induced by the local curvature of solid surfaces, we constructed a theoretical model which includes the Helfrich bending energy, the deformation energy of aggregates induced by solid surfaces, and the adsorption energy. The model calculations indicate that on highly curved solid surfaces the bending energy for bilayer structure sharply increases with surface curvature, which in turn induces the morphological transition from bilayer to cylindrical structure. Our results suggest that the local curvature provides a means of controlling the spatial organization of amphiphilic molecules.

Computer simulation studies on the interactions between nanoparticles and cell membrane

In recent times, nanoparticles (NPs) have received intense attention not only due to their potential applications as a candidate for drug delivery, but also because of their undesirable effects on human health. Although extensive experimental studies have been carried out in literature in order to understand the interaction between NPs and a plasma membrane, much less is known about the molecular details of the interaction mechanisms and pathways. As complimentary tools, coarse grained molecular dynamics (CGMD) and dissipative particle dynamics (DPD) simulations have been extensively used on the interaction mechanism and evolution pathway. In the present review we summarize computer simulation studies on the NP-membrane interaction, which developed over the last few years, and particularly evaluate the results from the DPD technique. Those studies undoubtedly deepen our understanding of the NP-membrane interaction mechanisms and provide a design guideline for new NPs.

Spontaneous insertion of GPI anchors into cholesterol-rich membrane domains

GPI-Anchored proteins (GPI-APs) can be exogenously transferred onto bilayer membranes both in vivo and in vitro, while the mechanism by which this transfer process occurs is unknown. In this work, we used atomistic molecular dynamics simulations and free energy calculations to characterize the essential influence of cholesterol on insertion of the GPI anchors into plasma membranes. We demonstrate, both dynamically and energetically, that in the presence of cholesterol, the tails of GPI anchors are able to penetrate inside the core of the lipid membrane spontaneously with a three-step mechanism, while in the absence of cholesterol no spontaneous insertion was observed. We ascribe the failure of insertion to the strong thermal fluctuation of lipid molecules in cholesterol-free bilayer, which generates a repulsive force in entropic origin. In the presence of cholesterol, however, the fluctuation of lipids is strongly reduced, thus decreasing the barrier for the anchor insertion. Based on this observation, we...

Pulling force and surface tension drive membrane fusion

Despite catalyzed by fusion proteins of quite different molecular architectures, intracellular, viral, and cell-to-cell fusions are found to have the essential common features and the nearly same nature of transition states. The similarity inspires us to find a more general catalysis mechanism for membrane fusion that minimally depends on the specific structures of fusion proteins. In this work, we built a minimal model for membrane fusion, and by using dissipative particle dynamics simulations, we propose a mechanism that the pulling force generated by fusion proteins initiates the fusion process and the membrane tension regulates the subsequent fusion stages. The model shows different features compared to previous computer simulation studies: the pulling force catalyzes membrane fusion through lipid head overcrowding in the contacting region, leading to an increase in the head-head repulsion and/or the unfavorable head-tail contacts from opposing membranes, both of which destabilize the contacting leaflets and thus promote membrane fusion or vesicle rupture. Our simulations produce a variety of shapes and intermediates, closely resembling cases seen experimentally. Our work strongly supports the view that the tight pulling mechanism is a conserved feature of fusion protein-mediated fusion and that the membrane tension plays an essential role in fusion.

Erythrocyte membrane skeleton inhibits nanoparticle endocytosis

Red blood cells (RBCs), also called erythrocytes, have been experimentally proposed in recent decades as the biological drug delivery systems through entrapping certain drugs by endocytosis. However, the internalization pathway of endocytosis seems to conflict with the robust mechanical properties of RBCs that is induced by the spectrin-actin network of erythrocyte membrane skeleton. In this work, we employed a minimum realistic model and the dissipative particle dynamics method to investigate the influence of the spectrin-actin membrane skeleton on the internalization of nanoparticles (NPs). Our simulations show that the existence of skeleton meshwork indeed induces an inhibiting effect that effectively prevents NPs from internalization. The inhibiting effect is found to depend on the membrane-NP attraction, skeleton tension and relative size of the NP to the membrane skeleton mesh. However, our simulations also demonstrate that there are two possibilities for successful internalization of NPs in the pre...

Exploring the shape deformation of biomembrane tubes with theoretical analysis and computer simulation

The shape deformation of membrane nanotubes is studied by a combination of theoretical analysis and molecular simulation. First we perform free energy analysis to demonstrate the effects of various factors on two ideal states for the pearling transition, and then we carry out dissipative particle dynamics simulations, through which various types of membrane tube deformation are found, including membrane pearling, buckling, and bulging. Different models for inducing tube deformation, including the osmotic pressure, area difference and spontaneous curvature models, are considered to investigate tubular instabilities. Combined with free energy analysis, our simulations show that the origin of the deformation of membrane tubes in different models can be classified into two categories: effective spontaneous curvature and membrane tension. We further demonstrate that for different models, a positive membrane tension is required for the pearling transition. Finally we show that different models can be coupled to effectively deform the membrane tube.

Membrane tube pearling induced by a coupling of osmotic pressure and nanoparticle adhesion

ABSTRACT In this work, a coarse-grained molecular dynamics simulation method that belongs to the class of dissipative particle dynamics scheme with implicit solvent was used to indicate that adsorption of nanoparticles (NPs) inside a lipid membrane tube and pressure difference across the membrane, e.g. osmotic pressure, cooperatively induce membrane tube pearling. We demonstrate that NP adsorption and aggregation initiate the shape transformation of the lipid tube, and pressure difference provides a driving force for pearling transition. Depending on the dynamic coupling of tube shape transition and NP aggregation in the interior of the tube, different shape transitions via four kinds of pearling pathways are recognised, including pearls on a string (i.e. vesicles are interconnected via either a chain or double-chain of NPs) and tube-to-vesicle transition that is dominated kinetically either by NP-membrane attraction or by pressure difference. Considering the fact that biological membranes are semipermeable and many proteins interact with the membranes, these findings not only provide a mechanism of membrane tube pearling but also demonstrate the importance of osmotic pressure and protein–membrane interaction for many cell activities related to shape transitions of biomembrane.