PowerPoint%20Presentation%20%20-%20%20Cell%20Sorting%20and%20Movement:%20Interplay%20of%20Chemotaxis%20and%20Cell%20Adhesion.

1
Modeling Chemotaxis, Cell Adhesion and Cell
Sorting. Examples with Dictyostelium
Eirikur Pálsson Dept of Biology, Simon Fraser
University
2
(No Transcript)
3
Examples of Processes Where Cell Movement Is
Important

• Throughout gastrulation and embryogenesis.
• In wound healing.
• Carcinoma cell invasion.
• Limb bud regeneration.
• Cell movement in Dictyostelium discoideum.

4
Purpose of a Cell Movement model

• Visualization of cell movements in 3-D
• Understand how simple cell-cell interactions,
  signaling and adhesion lead to complex cell
  movements
• Simplification Revealing the most important
  things
• Gives constraints. Suggests what behavior is
  possible

5
Outline

• Introduction
• Design of Model
• Results
• Conclusions Future Work

6
(No Transcript)
7
The Model.

• The basic unit of the model is an ellipsoidal
  cell
• Deformation of the cell depends on the history of
  the forces acting on it
• The cell conserves volume with variable
  ellipsoidal semi-axes
• The cell may adhere to other cells or to the
  substrate
• When the cell moves it sends out a pseudopod,
  attaches it to either a neighbor or the surface
• The cell responds to chemotactic signals

8
A Representation of the Deformability of Each Axis
9
dj
di
10
Rotation
11
Forces (static)
12
Force equations
Equation of motion
13
Temporal Evolution of the Model

• All the neighbor cells are found
• The chemical gradient around each cell is
  calculated
• The cells orient towards the chemical gradient
  and apply an active force in that direction
• All the forces acting on a cell are determined.
  These are of two types The passive and the
  active forces
• The cells are moved and deformed according to the
  equations of motion
• The chemical concentration is updated.

14
R Foty 1996
15
(No Transcript)
16
(No Transcript)
17
Sorting
Ebb gt Eab gtEaa



Random
Eab gt Eaa, Ebb
Separation
Eaa ,Ebb gt Eab
18
Color
Type
Adhesion
20.1
Limb Bud
Green
12.6
Pigm. Epith.
Red
8.5
Heart
Yellow
4.6
Liver
Blue
1.6
N. Retina
Orange
R Foty 1996
19
(No Transcript)
20
Sorting With or Without Random Cell Movement
Random Motion
Not Random
Sorting
Time
Sorting Changing Cell Stiffness and Adhesion
Normal Cell
Stiffer Cell
Sorting
Stiffer and more Adhesive Cell
Time
21
Sorting of Pre-spore and Pre-Stalk Cells
Takeuchi 1986
22
Sorting due to specific Cell Adhesion
23
Dictyostelium discoideum Life Cycle
24
Camp Waves During Aggregation
1 mm
K Lee Princeton U
25
Aggregation (Firtel)
26
(No Transcript)
27
Simulations of Dictyostelium discoideum
Aggregation in Response to cAMP signals.
28
Aggregation. Pacemaker Cells in Red
29
Aggregation. 1 to 1 Pacemaker Cells in Red
30
Aggregation,1-1. Reduced Diffusion
31
Bonner 1999
32
Simulations of 2-D slugs The Red Cells in the
front are cAMP Pacemakers
33
Slug with cAMP wave
34
Slug moving straight, Pacemaker graft
35
Cell Sorting.The Chemotactic force is 50
Larger in the Grey Cells
36
Slug with 2 different Cell types, same adhesion
37
Slug with 2 different cell types, specific cell
adhesion Grey cells more adhesive than green
38
Thicker Slug with 2 different cell types,
specific cell adhesion Grey cells more adhesive
than green
39
Thicker Slug with 2 different cell types,
specific cell adhesion Grey cells more adhesive
than green (Cross section)
40

• Conclusions
• The model reproduces well the observed behavior
  and properties of cell aggregates
• The chemotactic movement of cells in response to
  a cAMP wave are in qualitative agreement with
  experiments
• New Findings
• Random movement, cell stiffness and cell adhesion
  affect the rate of cell sorting
• Cell specific adhesion enhances chemotactic
  sorting and may be necessary to achieve cell
  sorting in a timely manner

41
(No Transcript)