Bo Song, Huajun Yuan, Cynthia Jameson, Sohail Murad, Chemical Engineering Department Primary Grant Support: US Department of Energy
Problem Statement and Motivation •
Understanding the interaction between nanoparticles and biological membrane is of significant importance in applications in cell imaging, biodiagnostics and drug delivery systems.
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Some basic questions explored: • How do nanoparticles transport? • What structural changes occur? • Can a lipid membrane heal?
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Use molecular dynamics simulations to develop better understanding of the transport process and characterization of nanoparticles.
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Investigate the elastic and dynamic properties of lipid membrane, during the permeation of the nanoparticles.
Key Achievements and Future Goals
Technical Approach • • • •
Used various sizes of nanocrystals as probes. Used coarse-grained dipalmitoylphosphatidy-lcholine (DPPC) lipid bilayers as a simple model membrane. Explored the transport of nanocrystal across DPPC lipid bilayers Investigated the changes in the structural and mechanical properties of DPPC bilayers during permeation.
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Used coarse-grained models to simulate nanoparticles and biomembrane systems successfully. Examined the permeation process of nanoparticles through lipid membranes and the response of lipid membrane at the fundamental molecular level. Explored the effect on transport across a lipid membrane arising from surface coatings on the nanoparticles.
Bo Song, Huajun Yuan, Cynthia Jameson, Sohail Murad, Chemical Engineering Department Primary Grant Support: US Department of Energy
Problem Statement and Motivation •
Understanding the nanoparticle permeation mediated water/ion penetration and lipid molecule flip-flops is of significant importance in drug delivery systems and cytoxicity.
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Some basic questions explored: • How many water molecules and ions may leak during nanoparticle permeation? • How do water and ion leakages depend on the physical properties of the nanoparticle and the surrounding environment? • How do individual lipid molecules respond when nanoparticle, water and ions permeate simultaneously?
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Use coarse-grained molecular dynamics simulations technology.
Key Achievements and Future Goals
Technical Approach • • •
Used bare gold nanoparticles as model nanoparticles. Coarse-grained dipalmitoylphosphatidy-lcholine (DPPC) lipid bilayers were used as a simple model membrane. Investigated the effect of NP size, permeation velocity, pressure and ion concentration gradient effects.
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Used coarse-grained models to simulate nanoparticles and biological membrane systems successfully.
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Examined the permeation process of nanoparticles through lipid membranes at the fundamental molecular level.
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Examined the water/ion penetration and lipid molecule flip-flop during the nanoparticle permeation.
Hongmei Liu, Cynthia Jameson and Sohail Murad, Chemical Engineering Department Primary Grant Support: US National Science Foundation
Problem Statement and Motivation •
Need for understanding transport of ions in biological membranes
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Understand the conduction mechanism of chloride ions in simpler models of ClC.
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Explain the permeation mechanisms of ions in such ClC ion channels.
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Validate our models with the experimental results, and then extend studies to more complex systems.
Key Achievements and Future Goals
Technical Approach •
Use molecular simulations to model the permeation of ions in chloride ion channels.
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Explained the molecular basis of conduction mechanisms of ions in ClC.
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Examine the effects of the architecture of the tube surface on the water molecules in the tube.
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Used this improved understanding to predict behavior of ions in ClC.
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Determine reorientation correlation times of water molecules of the first hydration shell of the ions in ion channels and in the bulk solution.
Used molecular simulation to explain the permeation mechanism of ions in ClC.
Huajun Yuan, Cynthia Jameson, Sohail Murad, Chemical Engineering Department Primary Grant Support: US Department of Energy
Problem Statement and Motivation •
Explore small molecules transport through membranes, to better understand a range of biological processes essential for life itself.
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Compare transport process of different gases.
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Compare gas permeability across different lipid membranes.
Model Lipid Membrane with embedded OmpA Protein Channel
Key Achievements and Future Goals
Technical Approach •
Develop an effective coarse-grained model to simulate gas transport across a model membrane with embedded OmpA protein channel.
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Validate model/method by comparing with atomistic simulations and experimental results.
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Compare transport of different gases across pure lipid membranes and lipid membranes embedded with OmpA.
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Predict behavior not studied experimentally.
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Simulated water channels with open and closed OmpA channels. Compared gas permeation with and without OmpA. Validated simulation results with experimental measurements on gas permeation.
Lewis E. Wedgewood, Chemical Engineering Department Primary Grant Support: National Science Foundation, 3M Company
Problem Statement and Motivation Brownian Dynamics Simulation of a Ferrofluid in Shear
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Establish The Mechanical Properties And Microstructure of Ferrofluids Under Flow Conditions
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Use Ferrofluids To Test New Theories Of Complex Fluids And The Relation Between Mircostructure And Flow Behavior
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Use The Resulting Models And Understanding To Develop Improved Ferrofluids And New Applications Such Targeted Drug Delivery
H Hey Key Achievements and Future Goals
Technical Approach •
Brownian Dynamics Simulations For Spherical And Slender Particles Is Used To Model The Microstructure Of Ferrofluids
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Improved Understanding Of The Behavior Of Ferrofluids Near Solid Boundaries And The Application Of Boundary Conditions
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LaGrange Multiplier Method Used To Satisfy Local Magnetic Field Effects
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Established Relation Between Applied Magnetic Fields And Ferrofluid Microstructure
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Computer Animation And Statistical Analysis To Characterize Particle Dynamics
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Development Of Constitutive Relations Suitable For Design Of New Applications
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Continuum Theory And Hindered Rotation Models To Model Mechanical Behavior
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Verification Of Hindered Rotation Theory And The Transport Of Angular Momentum In Complex Fluids
L.E. Wedgewood; Kyung-Hyo Kim, UIC Chemical Engineering
Problem Statement and Motivation
2.4+-0.1 1.0+-.08
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Understanding blood rheology (i.e., blood flow properties) is important for the treatment of occlusive vascular disease.
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Viscoelastic behavior of red blood cells affect flow behavior and transport in blood vesicles.
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A red blood cell is a biconcave disk with length of ~8.5um [Fig 1] and accounts for roughly 38% - 46% of blood’s volume.
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Fahraeus-Lindqvist effect: The decrease in apparent viscosity when blood vessel has small diameter less than about 0.3 mm [Fig 2].
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To develop a Brownian dynamics (BD) model that captures the essential rheological behavior of blood [Fig 3].
8.5+-0.4
Fig 1 Dimension of normal human with deviations Fig. 2.1- Dimensions with standard deviationsRBC of a normal wet standard human
Fig 2 RBC in a blood vessel
Fig 3 Simulation model of RBC
Key Achievements and Future Goals
Technical Approach •
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Construct a model for red blood cells suspended in blood plasma Fig. 3: • Bead-and-Spring Model: flexibility and elasticity of a red blood cell is represented by a network of springs to mimic cell membrane. • Intrinsic curvature of the membrane is modeled by bending potentials. • Membrane area and cell volume are constrained to be constant in accordance with actual cells. Complex flow calculations are made using Brownian dynamics simulations. Motion and configuration of red blood cells can be simulated in complex flow geometries.
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Results for a three bead-and-spring model gives a simplified view of the physical system, but captures the essential physical characteristics of red blood cells: • Correctly predicts the steady shearing properties giving the correct relation between shear stress and shear rate. • Correctly predicts the Fahraeus-Lindqvist effect for circular tubes of various radii.
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Future goals: • Addition of details to the red blood cell model: internal viscosity of cell, bending potentials and interaction between cells. • The method can be extended to more complex situations by replacing the single vessel for more complex geometries (walls, constriction, bends, junction, networks) or combinations.
L E Wedgewood, L C Nitsche, B Akpa: Chemical Engineering; R D Minshall, Pharmacology and Anesthesiology Primary Grant Support: National Institutes of Health
Problem Statement and Motivation Fig. 1 Caveolae are ~50 nm indentations at cell surfaces
Fig 2 Caveolae accept molecules to be absorbed into the cell (endocytosis)
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Animal cell membrane regions rich in the protein caveolin form ~50 nm pits or indentations (‘caveolae’) [Fig. 1]
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Caveolae accept molecular cargo that is to be absorbed by the cell, thus forming endocytic vesicles [Fig. 2] • roles in signaling, cholesterol trafficking, pathogen invasion • disruption of caveolin expression is linked to disease
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Current microscopic techniques cannot be used to continuously observe the process of formation of specific caveolae
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Coarse-grained approaches can be used to feasibly study interactions of caveolins with the lipid bilayer that result in the formation of caveolae [Figs. 3 and 4]
n rtransverse
rnormal Fig. 3 Increasingly coarse-grained models of lipid bilayer phospholipids
r
Fig. 4 A section-view of the membrane model
Key Achievements and Future Goals
Technical Approach •
The lipid bilayer is modeled as a coarse-grained 2D fluid [Fig. 3] • each particle in the model represents a cluster of phospholipids
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2D structure is preserved using a combination of potentials that [Fig. 4] • favor a specified minimum inter-particle distance • cause particles to be attracted to one another • penalize particles for leaving the 2D surface
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Computation is saved by only considering interactions with neighboring particles • particle interactions restricted to specified cutoff distances
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Caveolins modeled as bead-spring chains • subject to Brownian forces
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Lipid membrane modeled as a stable 2D fluid
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Various kinds of surfaces modeled • plane, sphere, hemisphere
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Physical properties of model are being investigated • to confirm that model exhibits typical lipid-bilayer characteristics
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Future goals • to incorporate caveolin proteins on the bilayer • to model the cytoskeleton and its interactions • to model the pinch-off of invaginated surface caveolae to form endocytic vesicles