Design of Lipid-Based Nanoparticle
A new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large-scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the self-assembly of a CPLS nanoparticle. The CPLS Nanoparticle is supposed to share the same biocompatibility as a liposome. Furthermore, the size of CPLS Nanoparticle is easily controlled by altering the polymer length and core size. More importantly, with the support from the PEGylated-core, the CPLS nanoparticle has higher stability in the shear flow.
Endocytosis mechanism of PEGylated Lipid-Based Nanoparticle
We compare the membrane wrapping process of a PEGylated rigid nanoparticle (NP) with a PEGylated liposome under identical conditions. Due to the mobility of grafted PEG polymers on the liposome's surface, the complete wrapping of a PEGylated liposome can be dramatically delayed and blocked, in comparison with a PEGylated rigid NP. For the first time, we observe the aggregation of PEG polymers in the contact region between a PEGylated liposome and the membrane, which in turn leads to a ligand-free region on the surface of the liposome during endocytosis. Subsequently, the partially wrapped PEGylated liposome can be bounced back to a less wrapped state. Through free energy analysis, we find that the aggregation of PEG polymers during the membrane wrapping process of a PEGylated liposome introduces a dramatic free energy penalty of about ∼800kBT, which is almost twice that of a PEGylated rigid NP. Such a large energy barrier and the existence of a ligand-free region on the surface of PEGlylated liposomes prevent their membrane wrapping, thereby reducing the chance of internalization by tumor cells. Therefore, our DPD simulation results provide a possible explanation for the inefficient cellular uptake of PEGylated liposomes.
Endocytosis mechanism of Elastic Nanoparticle
Using coarse-grained molecular dynamics simulations, we systematically investigate the receptor-mediated endocytosis of elastic nanoparticles (NPs) with different sizes, ranging from 25 to 100 nm, and shapes, including sphere-like, oblate-like, and prolate-like. Simulation results provide clear evidence that the membrane wrapping efficiency of NPs during endocytosis is a result of competition between receptor diffusion kinetics and thermodynamic driving force. The receptor diffusion kinetics refer to the kinetics of receptor recruitment that are affected by the contact edge length between the NP and membrane. The thermodynamic driving force represents the amount of required free energy to drive NPs into a cell. Under the volume constraint of elastic NPs, the soft spherical NPs are found to have similar contact edge lengths to rigid ones and to less efficiently be fully wrapped due to their elastic deformation. Moreover, the difference in wrapping efficiency between soft and rigid spherical NPs increases with their sizes, due to the increment of their elastic energy change. Furthermore, because of its prominent large contact edge length, the oblate ellipsoid is found to be the least sensitive geometry to the variation in NP’s elasticity among the spherical, prolate, and oblate shapes during the membrane wrapping.
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Mechanical properties of polymeric materials
Using coarse-grained molecular dynamics simulations, we investigate the size effect of carbon nanotube (CNT) lengths and graphene sheets on the mechanical properties of buckypapers and 3D graphene foams. Due to the different inter-molecular interactive mechanisms, we find that the size of element in the buckypaper and graphene foam greatly determine their mechanical properties.
