bright field

8
bright field fibronectin a SEM b d c e Fig. S1 EF Cap electrod e agar salt bridge Figure S1 Traction force analysis of cells in an EF. a Microfabrication of traction force detecting micropillar arrays. Silicon master (1) was used to fabricate a negative PDMS mold (2), then the positive PDMS pillars (3 and 4). The pillar arrays were coated with fibronectin (5 and 6), then cells were seeded onto the substrate (7). b Scanning electronic micrograph (SEM) of micropillar arrays. Scale bar = 20 µm. c Rhodamine conjugated- fibronectin-coated pillars were imaged in the bright field (left panel) and fluorescent channel (right panel). d A schematic drawing showing application of EFs to an electrotactic chamber. The area marked with black-dotted lines is shown in detail in (e). See details of the experimental procedure in Materials and Methods section.

Upload: vienna

Post on 13-Jan-2016

24 views

Category:

Documents


0 download

DESCRIPTION

bright field. fibronectin. SEM. a. b. c. d. e. agar salt bridge. electrode. EF. Cap. - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: bright field

bright field fibronectin

aSEM

b

d

c

e

Fig. S1

EF

Cap

electrode

agar salt bridge

Figure S1 Traction force analysis of cells in an EF. a Microfabrication of traction force detecting micropillar arrays. Silicon master (1) was used to fabricate a negative PDMS mold (2), then the positive PDMS pillars (3 and 4). The pillar arrays were coated with fibronectin (5 and 6), then cells were seeded onto the substrate (7). b Scanning electronic micrograph (SEM) of micropillar arrays. Scale bar = 20 µm. c Rhodamine conjugated-fibronectin-coated pillars were imaged in the bright field (left panel) and fluorescent channel (right panel). d A schematic drawing showing application of EFs to an electrotactic chamber. The area marked with black-dotted lines is shown in detail in (e). See details of the experimental procedure in Materials and Methods section.

Page 2: bright field

a No EF b

-200 mV/mm

c

0 2 4 6

-1.0-0.8-0.6-0.4-0.20.00.2

200 mV/mm No EF

Dir

ecte

dn

ess

(co

s ) Time (hr)

Fig. S2

Figure S2 Directional migration of MDCK cells in monolayer in an EF. a, b Representative plots of the velocity field for MDCK II cell monolayer based on particle image velocimetry (PIV) analysis. The arrows indicate the velocity vectors at different positions of the image. The velocity vectors are randomly oriented in the absence of EF whereas the velocity vectors show clear biased orientation toward the anode of an applied EF. c The directedness (cos θ) of MDCK II cell monolayer using the data from the PIV analysis.

Page 3: bright field

0.00.20.40.60.81.0

0

10

20

30

40

Mig

ratio

n sp

eed

(m

/h)

b MDCK I cells

Isolation Monolayer Isolation Monolayer

*

*C

oeffi

cien

t of

mov

emen

t effi

cien

cy

Fig. S3

0

20

40

0.00.20.40.60.81.0

Mig

ratio

n sp

eed

(m

/h)

Isolation Monolayer

*

c NRK cells

Isolation Monolayer

*

Coe

ffici

ent o

f m

ovem

ent e

ffici

ency

0

20

40

60

0.00.20.40.60.81.0

Mig

ratio

n sp

eed

(m

/h)

Isolation Monolayer Isolation Monolayer

*

d Tracheal epithelial cells

Coe

ffici

ent o

f m

ovem

ent e

ffici

ency

0

10

20

0.00.20.40.60.81.0

Mig

ratio

n sp

eed

(m

/h)

Isolation Monolayer

**

Coe

ffici

ent o

f m

ovem

ent e

ffici

ency

Isolation Monolayer

a MDCK II cells

Page 4: bright field

Figure S3 Electric fields increased migration efficiency in MDCK, NRK and tracheal epithelial cells. a Migration speed and migration efficiency of MDCK II cells in isolation and in a monolayer culture based on single cell tracking. EF = 200 mV/mm for 6 hours. b Migration speed and migration efficiency of MDCK I cells. EF = 200 mV/mm for 6 hours. c Migration speed and migration efficiency of NRK cells. EF = 200 mV/mm for 2 hours. d Migration speed and migration efficiency of tracheal epithelial cells in isolation and in monolayer. EF = 200 mV/mm for 30 minutes. Data are from at least 100 cells from 3 independent experiments and shown as Mean ± S.E.M. *, p<0.01 compared with cells in isolation. †, p<0.05 compared with cells in isolation. See Supplementary information, Video S2.

Page 5: bright field

0.00.20.40.60.81.01.2 Monolayer-50mV/mm

Isolation-50mV/mm

0.00.20.40.60.81.01.2 Monolayer-100mV/mm

Isolation-100mV/mm

Dire

cted

ness

(cos

)

0 10 20 30 40 50 60

Dire

cted

ness

(cos

)

Time in EF (min)0 10 20 30 40 50 60

Time in EF (min)

** * * * * * * * * * *

0h

-a

1h

-b

0h

-d

1h

-e

-50 150

sheet-50

-10 50

-30

-100

100

30

c

f

g h

m

m

0

30

60

90

0.00.20.40.60.81.0

Mig

ratio

n sp

eed

(m

/h)

Isolation Monolayer

i j

Isolation Monolayer

*

*

Coe

ffici

ent o

f m

ovem

ent e

ffici

ency

Fig. S4

Page 6: bright field

Figure S4 Collectively, bovine corneal epithelial cells migrate significantly more directionally in a physiological electric field. a-c Isolated bovine corneal epithelial cells (BCECs) migrated directionally to the cathode in an EF of 50 mV/mm for 1 hour. Lines and arrows represent migration paths and direction. d-f Monolayer BCECs migrated more directionally to the cathode in a field of the same strength. g, h Significantly higher migration directedness of cells in a monolayer than that of cells in isolation in both 50 and 100 mV/mm for 1 hour. i, j Migration speed and migration efficiency of BCECs in isolation and in monolayer in 50 mV/mm for 1 hour. Data are from at least 100 cells from 3 independent experiments and shown as mean ± S.E.M. *, p<0.01 compared with in isolation. Scale bars, 50 µm.

Page 7: bright field

-1.0-0.8-0.6-0.4-0.20.0

0

5

10

15

20

Dire

cted

ness

(cos

)

Mig

ratio

n sp

eed

(µm

/h)Vehicle Control Oleamide

Vehicle Control Oleamide *

*

e f

a b

Fig. S5

-150 50

-100

100

-150 50

-100

100c d

Cut edge Cut edge

Control Oleamide

- -

µm µm

J

H

Figure S5 Role of Gap junctions in collective electrotaxis. a, b MDCK I cells in a monolayer culture were scrape-loaded with Lucifer yellow dye, and the dye was efficiently transferred from dye-loaded cells to adjacent cells in control conditions (a), while little dye transfer was seen after cells were treated with oleamide (b). c, d Migration tracks of MDCK I cells in vehicle control or oleamide containing medium. e, f Migration directedness and speed of the cells in an EF with or without oleamide. EF = 200 mV/mm for 6 hours. Data are from at least 100 cells from 3 independent experiments and shown as Mean ± S.E.M. *, p<0.01 compared with vehicle control. Scale bars, 30 µm.

Page 8: bright field

00:50 - 03:15 05:45

+

a -

+

No EF

b c

0 2 4 65

10

15

20

25

Time (h)

No EF

Ave

rage

For

ce (n

N)

-

0 2 4 65

10

15

20

25

Time (h)

No EF

Ave

rage

For

ce (n

N)

-No EF

Forc

e D

irect

iona

lity

(Cos

)

0 2 4 6-0.8

-0.4

0.0

0.4

0.8

Time (h)

-No EF

Forc

e D

irect

iona

lity

(Cos

)

0 2 4 6-0.8

-0.4

0.0

0.4

0.8

Time (h)

-

Fig. S6

Figure S6 Isolated MDCK cells do not re-orient traction forces under an EF. a Time-lapse images of a GFP-tagged α5 integrin expressing cell on micro-fabricated pillar substrate. White arrow head and length indicate the direction and magnitude of traction forces, respectively. Time in hh:mm. b EF application did not change the directionality of traction force. c The average traction force of isolated cells showed little change under an applied EF. The data are shown as Mean ± S.E.M. EF = 200 mV/mm for 4 hours.