Lipid Vesicles in General Flows: The Numerical

Methods and the Influence of Reynolds Number

D. Salac

Mechanical and Aerospace Engineering

University at Buffalo, SUNY

MAE Seminar Series

Feb. 17, 2011
Lipid Bilayer Vesicles
Lipid Bilayer Vesicles
Lipid Bilayer Vesicles
Lipid Bilayer Vesicles
Lipid Bilayer Vesicles

Why are they interesting?

Vesicles as a Model System

Very Complex Structure

Over 50% lipids

(Eukaryotic Cells)
Vesicles as a Model System
Experiments have shown a similarity between the response of
biological cells and vesicles.

Shear Flow Conditions:

Abkarian and Viallat, 2008

Behavior of vesicles gives insight into behavior of biological

cells.
Possible Application: Drug Delivery System
Possible Application: Drug Delivery System

I How do these vesicles

migrate in response to flow
conditions in the body? Do
they congregate? Will they
get trapped?
Possible Application: Drug Delivery System

I How do these vesicles

migrate in response to flow
conditions in the body? Do
they congregate? Will they
get trapped?
I What type of shape changes
will occur? Will the vesicle
be able to withstand the
conditions in the body and
not break-up?
Properties of Vesicles

I Thickness of interface
is small.
I Constant enclosed
volume.
I Constant lipid number
(surface area).
I NOT a droplet.
 Goal:
1. Develop a model capable of
investigating the behavior of lipid
vesicles under a wide variety of
flow conditions.
2. Use this model to investigate flow
related to biological flows.
Outline:
1. Development of Model
2. Numerical Methods Used
3. Influence of Reynolds Number of
Vesicle Behavior
Development of Model
System Under Consideration

Enclosed fluid may be different

than ambiant fluid – Different
properties.
I u = Fluid velocity
I ρ = Fluid Density
I µ = Fluid Viscosity
Multiphase Flow Equations

In each fluid (k = i, o):

Duk
Momentum Equations: ρ =∇·σ
Dt
Stress: σ = −pk I + µ ∇uk + ∇T uk

Conservation of Volume: ∇ · uk = 0
Multiphase Flow Equations

In each fluid (k = i, o):

Duk
Momentum Equations: ρ =∇·σ
Dt
Stress: σ = −pk I + µ ∇uk + ∇T uk

Conservation of Volume: ∇ · uk = 0

On the interface:
Conservation of Area: ∇s · u = 0
Continuity of Velocity: [uo − ui ] = 0
Normal Stress Jump: [(σ o − σ i ) · n] = F
Interfacial Conditions

Energy of the membrane (Helfrich + tension):

Z  
1
E= bn κ2 + γ ds
Γ 2
Interfacial Conditions

Energy of the membrane (Helfrich + tension):

Z  
1
E= bn κ2 + γ ds
Γ 2

Generalized Laplace-Young jump condition:

δE
[σ · n] = F =
δΓ
Interfacial Conditions

Energy of the membrane (Helfrich + tension):

Z  
1
E= bn κ2 + γ ds
Γ 2

Generalized Laplace-Young jump condition:

δE
[σ · n] = F =
δΓ

Variational derivative of the energy:

 
δE 2 1 3
= γκn − ∇s γs + bn ∇s κ + κ n
δΓ 2
Description of the Interface: The Level Set Method
I φ acts as material
quantity.
I Interface moves by
advecting φ:
dφ
+ u · ∇φ = 0
dt
I Geometric quantities:
∇φ
n=
||∇φ||
κ = ∇s · n
∇s = (I − n ⊗ n) ∇
One-Fluid Continuum Model: Level Set + Navier-Stokes

Du
= −∇p + ∇ · µ ∇u + ∇T u



Navier-Stokes: ρ
Dt
+ δ(φ) (|∇φ|∇s γ − γκ∇φ)
 
2 1 3
+ bn δ(φ) ∇s κ + κ ∇φ
2
∂φ
Level Set: = −u · ∇φ
∂t
2D Scalings

Normalize with respect to outer fluid.

I Reduced Area: ν = 4Aπ/L2
I Viscosity Ratio: η = µin /µout
I Time: τ = µout R03 /bn
I Bending Number: Bn = (ρout bn )/(R0 µ2out )
I Shear Rate: χ = γ̇τ = γ̇µout R03 /bn
I Shear Flow Reynolds Number: Re = χBn
Reduced Area: ν = 4Aπ/L2

Begin with a circle with a given interface length:

ν = 1.0
Reduced Area: ν = 4Aπ/L2

Remove inner material while keeping the same interface length:

ν = 0.9
Reduced Area: ν = 4Aπ/L2

Remove inner material while keeping the same interface length:

ν = 0.7
Reduced Area: ν = 4Aπ/L2

Remove inner material while keeping the same interface length:

ν = 0.5
Reduced Area: ν = 4Aπ/L2

Remove inner material while keeping the same interface length:

ν = 0.3
2D Scalings

Normalize with respect to outer fluid.

I Reduced Area: ν = 4Aπ/L2
I Viscosity Ratio: η = µin /µout
I Time: τ = µout R03 /bn
I Bending Number: Bn = (ρout bn )/(R0 µ2out )
I Shear Rate: χ = γ̇τ = γ̇µout R03 /bn
I Shear Flow Reynolds Number: Re = χBn
2D Scalings

Normalize with respect to outer fluid.

I Reduced Area: ν = 4Aπ/L2
I Viscosity Ratio: η = µin /µout
I Time: τ = µout R03 /bn
I Bending Number: Bn = (ρout bn )/(R0 µ2out )
I Shear Rate: χ = γ̇τ = γ̇µout R03 /bn
I Shear Flow Reynolds Number: Re = χBn
2D Scalings

Normalize with respect to outer fluid.

I Reduced Area: ν = 4Aπ/L2
I Viscosity Ratio: η = µin /µout
I Time: τ = µout R03 /bn
I Bending Number: Bn = (ρout bn )/(R0 µ2out )
I Shear Rate: χ = γ̇τ = γ̇µout R03 /bn
I Shear Flow Reynolds Number: Re = χBn

Normalized Navier-Stokes:
D û 1
∇ · µ̂ ∇û + ∇T û



ρ̂ = − ∇p̂ +
Dt Bn  
1 2 1 3
+ δ(φ) (|∇φ|∇s γ̂ − γ̂κ̂∇φ) + δ(φ) ∇s κ̂ + κ̂ ∇φ
Bn 2
Numerical Methods
The General Steps

To advance forward in time do:

1. Advance the interface – Level Set Advection
2. Reinitialize the level set – Augmented FMM
3. Advance the fluid field – 4-Step Splitting Scheme
4. Adjust the grid
The General Steps

To advance forward in time do:

1. Advance the interface – Level Set Advection
2. Reinitialize the level set – Augmented FMM
3. Advance the fluid field – 4-Step Splitting Scheme
4. Adjust the grid
Level Set Advection

∂φ
The goal: To solve ∂t + u · ∇φ = 0 accurately and
quickly.
Level Set Advection

∂φ
The goal: To solve ∂t + u · ∇φ = 0 accurately and
quickly.
Use the method given in “A gradient-augmented
level set method with an optimally local, coherent
advection scheme”, Nave, Rosales, and Seibold,
JCP 229 (2010), 3802-3827.
Level Set Advection: Augmented Lagrangian Level Set

Solve both for the level set function, φ, and the

gradient field ψ = ∇φ using Lagrangian methods:
Dφ
=0
Dt
Dψ
= −∇u · ψ
Dt
Level Set Advection: Augmented Lagrangian Level Set

Step 1: Determine the departure location xd = x − ∆tun+1 .

Level Set Advection: Augmented Lagrangian Level Set

Step 2: Interpolate φd = φn (xd ) and ψd = ψn (xd ).

Level Set Advection: Augmented Lagrangian Level Set

Step 3: Set values φn+1 = φd and ψn+1 = (I − ∆t∇un+1 ) · ψd .

The General Steps

To advance forward in time do:

1. Advance the interface – Level Set Advection
2. Reinitialize the level set – Augmented FMM
3. Advance the fluid field – 4-Step Splitting Scheme
4. Adjust the grid
Signed Distance Function
Level Set Reinitialization

I Signed distance function generally have the best properties

for level set based calculations.
I All signed distance functions have the property of
|∇φ| = 1.
I Over time the level set may lose this property.
I To address this the periodic replacement with a signed
distance function is needed.
Level Set Reinitialization

I Signed distance function generally have the best properties

for level set based calculations.
I All signed distance functions have the property of
|∇φ| = 1.
I Over time the level set may lose this property.
I To address this the periodic replacement with a signed
distance function is needed.

Goal: To construct a signed distance function

without moving the original interface.
FMM

Evolution equation for the Fast Marching Method

(Sethian, PNAS 1996):
F |∇φ| = 1

I Valid if F is of one sign everywhere.

I Solve by an ordered list beginning at the
interface.
I Efficient, solving in time O(N log N)
I For reinitialization set F = 1 and solve to
enforce |∇φ| = 1 at all grid points.
FMM

1. Explicitly calculate φ next to

the interface.
FMM

1. Explicitly calculate φ next to

the interface.
2. Update nodes in an ordered
manner – The nodes closer
to the interface before those
farther away.
Issue with FMM

The standard FMM does not give a smooth level set field –
Curvature and derivatives of curvature are very noisy.
Solution: The Augmented FMM

Enforce the following at every grid point:

1. ∇φ · ∇φ = 1
2. ∇ (∇φ · ∇φ) = 0
3. ∇∇ (∇φ · ∇φ) = 0
Solution: The Augmented FMM

Enforce the following at every grid point:

1. ∇φ · ∇φ = 1
2. ∇ (∇φ · ∇φ) = 0
3. ∇∇ (∇φ · ∇φ) = 0

In 2D gives φ, φx , φy , φxx , φyy , φxy .

Augmented FMM
Results in a smooth curvature field for a given shape.
The General Steps

To advance forward in time do:

1. Advance the interface – Level Set Advection
2. Reinitialize the level set – Augmented FMM
3. Advance the fluid field – 4-Step Splitting Scheme
4. Adjust the grid
Normalized Navier-Stokes

Du 1
∇ · µ ∇u + ∇T u



ρ = − ∇p +
Dt Bn
+ δ(φ) (|∇φ|∇s γ − γκ∇φ)
 
1 1
+ δ(φ) ∇2s κ + κ3 ∇φ
Bn 2

Use a splitting scheme to solve.

3-step Navier-Stokes Splitting

Approximate velocity based on explicit quantities.

û1 − und
1. ρ =
∆t
∇ · µ∇ u + bn ∇2s κ + 12 κ3 δ(φ)∇φ + δ(φ) (|∇φ|∇s γ n − γ n κ∇φ)
T n



3-step Navier-Stokes Splitting

Solve for the pressure using divergence-free condition.

û1 − und
1. ρ =
∆t
∇ · µ∇ u + bn ∇2s κ + 12 κ3 δ(φ)∇φ + δ(φ) (|∇φ|∇s γ n − γ n κ∇φ)
T n

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain
3-step Navier-Stokes Splitting

Perform semi-implicit update for stability.

û1 − und
1. ρ =
∆t
∇ · µ∇ u + bn ∇2s κ + 12 κ3 δ(φ)∇φ + δ(φ) (|∇φ|∇s γ n − γ n κ∇φ)
T n

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain

un+1 − û2

3. ρ = ∇ · µ∇un+1
∆t
3-step Navier-Stokes Splitting

Perform semi-implicit update for stability.

û1 − und
1. ρ =
∆t
∇ · µ∇ u + bn ∇2s κ + 12 κ3 δ(φ)∇φ + δ(φ) (|∇φ|∇s γ n − γ n κ∇φ)
T n

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain

un+1 − û2

3. ρ = ∇ · µ∇un+1
∆t

How do you apply ∇s · u = 0?

4-step Navier-Stokes Splitting

Approximate velocity based on explicit quantities.

û1 − und
= ∇ · µ∇T un + bn ∇2s κ + 12 κ3 δ(φ)∇φ



1. ρ
∆t
4-step Navier-Stokes Splitting

Solve for the pressure using divergence-free condition.

û1 − und
= ∇ · µ∇T un + bn ∇2s κ + 12 κ3 δ(φ)∇φ



1. ρ
∆t

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain
4-step Navier-Stokes Splitting

Perform semi-implicit update for stability.

û1 − und
= ∇ · µ∇T un + bn ∇2s κ + 12 κ3 δ(φ)∇φ



1. ρ
∆t

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain

û3 − û2
3. ρ = ∇ · (µ∇û3 )
∆t
4-step Navier-Stokes Splitting

Solve for the tension to enforce surface incompressibility.

û1 − und
= ∇ · µ∇T un + bn ∇2s κ + 12 κ3 δ(φ)∇φ



1. ρ
∆t

û2 − û1
2. ρ = −∇p n+1
∆t
∇ · u = 0 in the domain

û3 − û2
3. ρ = ∇ · (µ∇û3 )
∆t

un+1 − û3

4. ρ = δ(φ) |∇φ|∇s γ n+1 − γ n+1 κ∇φ
∆t
∇s · u = 0 on the interface
Solve for γ

To determine γ use the Closest Point Method

(Macdonald and Ruuth, 2008 & Macdonald and
Ruuth, 2009)
The Closest Point

Let cp(x) be the closest point in the interface to grid point x.

Three Principles

1. ∇s u(x) = ∇(u(cp(x))).
Three Principles

1. ∇s u(x) = ∇(u(cp(x))).

2. ∇s · v(x) = ∇ · (v(cp(x))).
Three Principles

1. ∇s u(x) = ∇(u(cp(x))).

2. ∇s · v(x) = ∇ · (v(cp(x))).

3. A surface PDE and body PDE will agree on the

surface provided the body PDE is obtained from
the surface PDE by using the principles above.
Example Discritization: Surface Laplacian

I Discritize ∇2s u on a surface S embedded in Ω.

Example Discritization: Surface Laplacian

I Discritize ∇2s u on a surface S embedded in Ω.

I In Ω: ∇2s u = ∇2 (u(cp(x))).
Example Discritization: Surface Laplacian

I Discritize ∇2s u on a surface S embedded in Ω.

I In Ω: ∇2s u = ∇2 (u(cp(x))).

I Discritization:
1
∇2s u(xi,j ) = (u(cp(xi+1,j )) + u(cp(xi−1,j )) − 4u(cp(xi,j ))
h2
+ u(cp(xi,j+1 )) + u(cp(xi,j−1 )))
Example Discritization: Surface Laplacian

I Discritize ∇2s u on a surface S embedded in Ω.

I In Ω: ∇2s u = ∇2 (u(cp(x))).

I Discritization:
1
∇2s u(xi,j ) = (u(cp(xi+1,j )) + u(cp(xi−1,j )) − 4u(cp(xi,j ))
h2
+ u(cp(xi,j+1 )) + u(cp(xi,j−1 )))

How do we calculate u(cp(xi,j ))?

Interpolation

Evaluate u(cp(xi,j )) using barycentric Lagrange interpolation.

Interpolation + PDE

Replace u(cp(xi,j )) in the discritized PDE with interpolant.

Interpolation + PDE

Replace u(cp(xi,j )) in the discritized PDE with interpolant.

Apply to Membrane Tension

I The PDE to solve on the interface is

γκ2 − ∇2s γ = ∇s · u.
Apply to Membrane Tension

I The PDE to solve on the interface is

γκ2 − ∇2s γ = ∇s · u.

I Use second-order derivative approximation and

third-order interpolation – Overall method
should be second order.
Apply to Membrane Tension

I The PDE to solve on the interface is

γκ2 − ∇2s γ = ∇s · u.

I Use second-order derivative approximation and

third-order interpolation – Overall method
should be second order.

I Discritizing the PDE results in a sparse matrix -

Use any available method to solve.
The General Steps

To advance forward in time do:

1. Advance the interface – Level Set Advection
2. Reinitialize the level set – Augmented FMM
3. Advance the fluid field – 4-Step Splitting Scheme
4. Adjust the grid
Non-Graded Cartesian Grid
Place grid points only where they need to go based on:
1. Position of interface
2. Fluid conditions at a point
Influence of Reynolds Number
of Vesicle Behavior
Initial Configuration: χ = 1
Configuration at t > t0 : χ = 1
Tumbling vs. Tank Treading
Tumbling vs. Tank Treading
Traditional Tank-Treading/Tumbling Transition
Traditional Tank-Treading/Tumbling Transition
ν = 0.6, Re = 1 × 10−4 , η = 8.0
ν = 0.6, Re = 1 × 10−4 , η = 8.0
ν = 0.6, Re = 4 × 10−1 , η = 8.0
ν = 0.6, Re = 4 × 10−1 , η = 8.0
ν = 0.6, Re = 6 × 10−1 , η = 8.0
ν = 0.6, Re = 6 × 10−1 , η = 8.0
ν = 0.8, Re = 1, η = 15.0: Damped Tank-Treading
ν = 0.8, Re = 1, η = 15.0: Damped Tank-Treading
Tank Treading/Tumbling Transition: ν = 0.6
Tank Treading/Tumbling Transition: ν = 0.7
Tank Treading/Tumbling Transition: ν = 0.8
Tank Treading/Tumbling Transition: ν = 0.9
Tank Treading/Tumbling Transition: ν = 0.6 to ν = 0.9
Tank Treading/Tumbling Transition: ν = 0.6 to ν = 0.9
Why does this happen?

v = 0.60 Re = 1 × 10−4 ν=1

Why does this happen?

v = 0.60 Re = 1 × 10−4 ν=8

Why does this happen?

v = 0.60 Re = 6 × 10−1 ν=8

Thank You!