Biomedical Engineering Reference
In-Depth Information
a
b
Top layer
O X
X
X X
O
X
O
X
Semi-permeable
membrane
200 µm
Bottom layer
Seed cell type 1
Seed cell type 2
Seed cell type 3
1 h
10 h
20 h
c
200 µm
L12
X4
X7
FIGURE 6.31
Chemotactic. gradients. created. by. CXCL12. source-sink. cells.. In. panel. (c),. “L12”.
denotes. the. CXCL12-secreting. cells. (labeled. with. CellTracker. red),. “X4”. the. CXCR4-expressing.
cells.(nuclear-labeled.with.Hoechst,.in.blue),.and.“X7”.the.CXCR7-expressing.cells.(labeled.with.
CellTracker.green)..(From.Yu-suke.Torisawa,.Bobak.Mosadegh,.Tommaso.Bersano-Begey,.Jessica.
M.. Steele,. Kathryn. E.. Luker,. Gary. D.. Luker,. and. Shuichi. Takayama,. “Microluidic. platform. for.
chemotaxis. in. gradients. formed. by. CXCL12. source-sink. cells,”.
Integr. Biol.
. 2,. 680-686,. 2010..
Reproduced.with.permission.from.The.Royal.Society.of.Chemistry.)
he chemokine CXCL12 has been proposed to promote metastasis in breast cancer and var-
ious other malignancies. CXCL12 is secreted by ibroblasts in primary human breast tumor.
CXCL12 binds to receptor CXCR4 on breast cancer cells to promote chemotaxis, and also to
receptor CXCR7 (expressed by stromal cells and subsets of breast cancer cells), but the role of
CXCR7 in CXCL12-dependent chemotaxis is not well understood. Shuichi Takayama and col-
leagues at the University of Michigan have built a microluidic system to test a hypothesis for the
possible role of CXCR7-expressing cells (
Figure 6.31
). According to the “sink-source” hypoth-
esis (based on a zebraish observation), the CXCR7-expressing cells act as a sink to sequester the
CXCL12 chemokine, and chemotaxis of CXCR4-expressing cells toward CXCL12-expressing
cells (chemokine source) is critically dependent on the presence and location of the sink cells.
Takayama and coworkers veriied this hypothesis using their hydrodynamic trapping technol-
ogy (see Section 2.6.2.6), whereby cells are trapped when a cell suspension is forced through a
porous membrane (the cells do not it through the pores of the membranes, so they get trapped
on top of the membrane). he membrane supports cell culture and cell migration.
6.4.2.3 Bacterial Cell Migration
Bacterial chemotaxis is very diferent from chemotaxis of adherent cells and, consequently, the
engineering challenges associated with investigating bacteria are also very diferent. Bacteria
move in three-dimensional space in a biased random walk, constantly sampling their local
microenvironment. hey propel themselves with one or more lagella into straight trajectories
called “runs” or erratic reorientation events called “tumbles,” depending on which direction
the molecular motors (that drive the lagella ilaments) turn. To achieve gradient sensing, the
cell simply modulates the fraction of time spent tumbling or running by doing a temporal com-
parison: the receptor occupancy in the past is compared to that in the more distant past. he
