Cellular and Molecular Bioengineering

, Volume 7, Issue 1, pp 122–135 | Cite as

The Number of Lines a Cell Contacts and Cell Contractility Drive the Efficiency of Contact Guidance

  • Nicholas R. Romsey
  • Yue Hou
  • Laura Lara Rodriguez
  • Ian C. SchneiderEmail author


Cell migration is an important biological function that impacts many physiological and pathological processes. Often migration is directed along aligned fibers of collagen at different densities, a process called contact guidance. However, cells adhere to other components in the extracellular matrix, possibly affecting migrational behavior. Additionally, changes in intracellular contractility are well known to affect random migration, but its effect on contact guidance is less known. This study examines differences in directed migration in response to variations in the spacing of collagen, non-specific background adhesion strength and myosin II-mediated contractility. Collagen was microcontact printed onto glass substrates and timelapse live-cell microscopy was used to measure migration characteristics. Increasing the number of lines a cell contacts or decreasing contraction led to decreases in directionality, but speed changes were context dependent. This suggests that while cell migration speed is a biphasic function of contractility, directionality appears to be a monotonic, increasing function of contractility. Thus, increasing the number of lines a cell contacts or decreasing contractility degrades the contact guidance fidelity.


Directed cell migration Carcinoma Microcontact printing Collagen Paxillin and blebbistatin 



Extracellular matrix


Collagen type I


Poly-l-lysine polyethylene glycol






Focal adhesion



The authors thank Caroline Zahler for initiating the project during an NSF REU (EEC-1156933) experience and Dave Schmidt and Yong Luo for technical help. The authors acknowledge support from the Roy J. Carver Charitable Trust for general project funding and from NSF ARI-R2 (CMMI-0963224) for funding the renovation of the research laboratories used for these studies.

Supplementary material

12195_2013_299_MOESM1_ESM.avi (3.7 mb)
Video of the cell shown in Fig. 1A. Collagen lines are presented as green. The length of the video spans roughly 10 h. (AVI 3806 kb)
12195_2013_299_MOESM2_ESM.avi (5.3 mb)
Video of the cell shown in Fig. 2A. Collagen lines are presented as green. The length of the video spans roughly 10 h.(AVI 5386 kb)
12195_2013_299_MOESM3_ESM.avi (2.7 mb)
Video of the cell shown in Fig. 2B. Collagen lines are presented as green. The length of the video spans roughly 6 h. AVI 2801 kb)
12195_2013_299_MOESM4_ESM.avi (3.1 mb)
Video of the cell shown in Fig. 2C. Collagen lines are presented as green. The length of the video spans roughly 7 h. (AVI 3182 kb)
12195_2013_299_MOESM5_ESM.avi (11.6 mb)
Video of the cell shown in Fig. 4A. Collagen lines are presented as red and paxillin-EGFP as green. The length of the video spans roughly 1 h. (AVI 11920 kb)
12195_2013_299_MOESM6_ESM.avi (13.7 mb)
Video of the cell shown in Fig. 4B. Collagen lines are presented as red and paxillin-EGFP as green. The length of the video spans roughly 1 h. (AVI 14047 kb)
12195_2013_299_MOESM7_ESM.avi (2.7 mb)
Video of the cell shown in Fig. 8A. Collagen lines are presented as green. The length of the video spans roughly 9 h. (AVI 2742 kb)
12195_2013_299_MOESM8_ESM.avi (3.6 mb)
Video of the cell shown in Fig. 8B. Collagen lines are presented as green. The length of the video spans roughly 8 h.(AVI 3686 kb)
12195_2013_299_MOESM9_ESM.avi (1003 kb)
Video of the cell shown in Fig. 8C. Collagen lines are presented as green. The length of the video spans roughly 8 h. (AVI 1002 kb)
12195_2013_299_MOESM10_ESM.avi (3.4 mb)
Video of the cell shown in Fig. 8D. Collagen lines are presented as green. The length of the video spans roughly 6 h. (AVI 3441 kb)
12195_2013_299_MOESM11_ESM.avi (10.3 mb)
Video of a cell migrating on 3x5 collagen lines backfilled with fibronectin from Fig. S2. Fibronectin backfill is presented as green. The length of the video spans roughly 7 h. (AVI 10563 kb)
12195_2013_299_MOESM12_ESM.avi (9.4 mb)
Video of a cell migrating on 3x10 collagen lines backfilled with fibronectin from Fig. S2. Fibronectin backfill is presented as green. The length of the video spans roughly 7 h. (AVI 9581 kb)
12195_2013_299_MOESM13_ESM.tif (140 kb)
Fig. S1 Cell Adhesion Strength: Cells were plated on unpatterned substrates as described in the “Materials and Methods” section and spun in media. Cell number was counted before and after spinning and the fraction remaining was normalized to the largest fraction (Col:PLL) (n samples = 2 and n images = 10). Error bars represent 95% confidence intervals. (TIFF 140 kb)
12195_2013_299_MOESM14_ESM.tif (972 kb)
Fig. S2 Directionality and cell migration speed on Col:FN substrates: A. Directionality and B. cell migration speed are shown for various line spacing widths and backfill molecules. Data is similar to Fig. 5 with the addition of FN backfilled substrates. Col:FN: 3x5 μm (n cells = 14 and n substrates = 1) and 3x10 μm (n cells = 15 and n substrates = 1). C. Directionality and D. cell migration speed is plotted as a function of the number of lines over which a cell spans. Col:FN: low (n cells = 6 and n substrates = 2), medium (n cells = 8 and n substrates = 1) and high (n cells = 11 and n substrates = 2). Number of lines (< 3, low; 3-5, medium; > 5, high). Col:PLL-PEG (circles), Col:PLL (squares) and Col:FN (triangles). Lines guide the eyes and error bars are 95% confidence intervals. (TIFF 973 kb)


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Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • Nicholas R. Romsey
    • 1
  • Yue Hou
    • 1
  • Laura Lara Rodriguez
    • 1
  • Ian C. Schneider
    • 1
    • 2
    Email author
  1. 1.Department of Chemical and Biological EngineeringIowa State UniversityAmesUSA
  2. 2.Department of Genetics, Development and Cell BiologyIowa State UniversityAmesUSA

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