Surface rheology of block-copolymer stabilized interfaces: a combined computational & experimental study. SNF project 200021_156106 at www.complexfluids.ethz.ch/snf15
The PEGylated liposome, composed of an aqueous core and a fluid state lipid bilayer shell, is one of the few Food and Drug Administration (FDA) approved drug delivery platforms. To prevent the absorption of serum proteins, the surface of a liposome is decorated by hydrophilic and bio-compatible polyethylene glycol (PEG) polymers, which can significantly extend the blood circulation time of liposomes. In this work, with the help of dissipative particle dynamics (DPD) simulations, we explore how the tethered PEG polymers will affect the membrane wrapping process of PEGylated liposomes during endocytosis. Specifically, 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 approximate to 800k(B)T, which is almost twice that of a PEGylated rigid NP. Here k(B) and T are the Boltzmann constant and temperature, respectively. 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. In addition, we suggest that by increasing the repulsive interactions between grafted PEG polymers it might be possible to limit their aggregation, and in turn, facilitate the internalization of PEGylated liposomes. The current study provides fundamental insights into the endocytosis of PEGylated liposomes, which could help to design this platform with high efficacy for drug delivery. Kroger, Martin/C-1946-2008; Shen, Zhiqiang/O-5073-2019; Li, Ying/B-9378-2008 Kroger, Martin/0000-0003-1402-6714; Shen, Zhiqiang/0000-0003-0804-2478; Li, Ying/0000-0002-1487-3350 Department of Mechanical Engineering at the University of Connecticut; GE Fellowship for innovation; National Science Foundation [ACI-1053575]; Swiss National Science Foundation [200021_156106] Z. S., H. Y. and Y. L. are grateful for support from the Department of Mechanical Engineering at the University of Connecticut. Z. S. is thankful for partial financial support from the GE Fellowship for innovation. Z. S. thanks Jiuling Wang for the insightful discussions about the PSO algorithm. This research benefited in part from the computational resources and staff contributions provided for Booth Engineering Center for Advanced Technology (BECAT) at the University of Connecticut. A part of this work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575. The contribution by M. K. was promoted by the Swiss National Science Foundation through grant 200021_156106. [hide]
Principal Investigators
Leonard Sagis (PL)
Polymer Physics, ETH Zurich, Switzerland ►
Wageningen University, Netherlands ►
Patrick Ilg (PL)
Polymer Physics, ETH Zurich, Switzerland ►
University of Reading, United Kingdom ►
Peter Fischer (Co-PI)
Inst. Food, nutrition and health, ETH Zurich, Switzerland ►
Martin Kröger (PI)
Polymer Physics, ETH Zurich, Switzerland ►
Secretary
Patricia Horn
Polymer Physics, ETH Zurich, Switzerland ►
Involved Students
Ahmad Moghimikheirabadi
Polymer Physics, ETH Zurich, Switzerland ►
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Selected conferences (co-)organized by project members
IWNET 2015
05 Jul - 10 Jul 2015, 7th International workshop on nonequilibrium thermodynamics (IWNET 2015), Hilvarenbeek, The Netherlands ►
learn more ► About this project
Complex fluid-fluid interfaces are interfaces in which the adsorbed species self-assemble into complex microstructures. Such interfaces are ubiquitous in nature, industrial processes, and consumer products, and can be found in living cells, nano- and microcapsules, vesicles, food emulsions, or foam. Compared to simple liquid-like interfaces (stabilized by low molecular weight surfactants), complex interfaces display significant viscoelasticity, with high values for their surface shear and dilatational moduli. Their stress-deformation behavior dominates the macroscopic dynamics of multiphase materials that contain such interfaces, and when this occurs those materials can be referred to as Interface-Dominated Materials (IDMs).Complex interfaces can be formed by a wide range of surface active components, such as proteins, colloidal particles, polymers, lipids, or mixtures of these components. In this proposal we will focus on complex interfaces stabilized by amphiphilic multi-block copolymers. These polymers consist of alternating blocks of a hydrophilic repeating unit A, and a hydrophobic repeating unit B. Amphiphilic copolymers can form interfaces with exceptional mechanical properties. This makes them ideal candidates for application in highly stable emulsions, or encapsulation systems with high mechanical stability, for application in food and pharmaceutical products.
Amphiphilic copolymers may form 2d gels, 2d (soft) glass phases, 2d (liquid) crystalline phases, or even 2d metastable emulsions (phase-separated mixtures of immiscible copolymers) after adsorption. The type of structure formed depends on surface concentration, and length, distribution, rigidity, and hydrophobicity of the sub-blocks of the copolymer. The response of polymer stabilized fluid-fluid interfaces to deformations or gradients in temperature is often highly nonlinear. The nonlinearity in their response to perturbations is a result of changes in this interfacial microstructure, induced by the applied gradients. The effect of deformations on interfacial microstructure, and the effect of these changes on macroscopic dynamics of interface-dominated materials is still poorly understood. A more fundamental understanding of the nonlinear response of polymer interfaces, is essential for a targeted design of high-end polymer stabilized IDMs, such as encapsulation systems with environmental triggers, nanoparticles with structured interfaces, or foam and emulsions with extreme stability. In view of the widespread occurrence of IDMs, the study of dynamic mechanical properties of these interfaces is highly relevant for many disciplines, such as colloid and interface science, physical chemistry, polymer physics, pharmaceutical science, food science, coating technology, or soft matter physics.
The aim of this project is to characterize the microstructure and mechanical properties of interfaces stabilized by multi-block copolymers, using a multiscale multidisciplinary approach, which integrates state of the art computational methods with surface rheological experiments, and experimental interfacial structure evaluation. The computational modeling will be done using Monte Carlo (MC) and Molecular Dynamics (MD) simulations. We will measure both shear and dilatational surface properties, and the microstructure will be evaluated using various forms of microscopy (AFM, TEM, SEM), and neutron and X-ray reflectivity measurements. We will determine the mechanical properties and interfacial structure as a function of surface polymer concentration, chemical structure of the polymers (variation of number, size, and distribution of blocks), and degree of hydrophobicity and rigidity of the sub-blocks. A detailed insight in the dynamic behavior of copolymer interfaces will provide new insight in the macroscopic dynamic behavior of polymer stabilized interface-dominated materials (emulsions, foam, encapsulation systems, nanoparticles), and will allow a more targeted design of these systems with tailor made properties, tuned for specific industrial applications.
29 April 2024 mk