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PMID: 25719270 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Statistical analysis of cell migration in 3D using the anisotropic persistent random walk model.

Nature protocols ·Vol. 10 ·No. 3 ·2015-03-00 ·Pages 517-27

Wu PH, Giri A, Wirtz D

Abstract

Cell migration through 3D extracellular matrices (ECMs) is crucial to the normal development of tissues and organs and in disease processes, yet adequate analytical tools to characterize 3D migration are lacking. The motility of eukaryotic cells on 2D substrates in the absence of gradients has long been described using persistent random walks (PRWs). Recent work shows that 3D migration is anisotropic and features an exponential mean cell velocity distribution, rendering the PRW model invalid. Here we present a protocol for the analysis of 3D cell motility using the anisotropic PRW model. The software, which is implemented in MATLAB, enables statistical profiling of experimentally observed 2D and 3D cell trajectories, and it extracts the persistence and speed of cells along primary and nonprimary directions and an anisotropic index of migration. Basic computer skills and experience with MATLAB software are recommended for successful use of the protocol. This protocol is highly automated and fast, taking <30 min to analyze trajectory data per biological condition.

MeSH Terms
Anisotropy Cell Movement/physiology Cellular Microenvironment/physiology Imaging, Three-Dimensional/methods Models, Biological Stochastic Processes
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wu Pei-Hsun
1] Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA. [2] Johns Hopkins Physical Science Oncology Center, The Johns Hopkins University, Baltimore, Maryland, USA.
Giri Anjil
1] Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA. [2] Johns Hopkins Physical Science Oncology Center, The Johns Hopkins University, Baltimore, Maryland, USA.
Wirtz Denis
1] Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA. [2] Johns Hopkins Physical Science Oncology Center, The Johns Hopkins University, Baltimore, Maryland, USA. [3] Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. [4] Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. [5] Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
References (33)
33 references, click to expand
  1. Elucidating the role of matrix stiffness in 3D cell migration and remodeling.
    Biophys J. 2011 Jan 19;100(2):284-93 PMID: 21244824
  2. A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations.
    J Cell Biol. 1988 Feb;106(2):303-9 PMID: 3339093
  3. Loss of Scar/WAVE complex promotes N-WASP- and FAK-dependent invasion.
    Curr Biol. 2013 Jan 21;23(2):107-17 PMID: 23273897
  4. The physics of cancer: the role of physical interactions and mechanical forces in metastasis.
    Nat Rev Cancer. 2011 Jun 24;11(7):512-22 PMID: 21701513
  5. Migration of individual microvessel endothelial cells: stochastic model and parameter measurement.
    J Cell Sci. 1991 Jun;99 ( Pt 2):419-30 PMID: 1885678
  6. The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3-dimensional cancer cell migration.
    FASEB J. 2013 Oct;27(10):4089-99 PMID: 23796785
  7. A novel approach to high accuracy of video-based microrheology.
    Biophys J. 2009 Jun 17;96(12):5103-11 PMID: 19527670
  8. Cell motility as persistent random motion: theories from experiments.
    Biophys J. 2005 Aug;89(2):912-31 PMID: 15951372
  9. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis.
    J Cell Biol. 2003 Jan 20;160(2):267-77 PMID: 12527751
  10. Cellular motility driven by assembly and disassembly of actin filaments.
    Cell. 2003 Feb 21;112(4):453-65 PMID: 12600310
  11. Integrins: roles in cancer development and as treatment targets.
    Br J Cancer. 2004 Feb 9;90(3):561-5 PMID: 14760364
  12. Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis.
    Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94 PMID: 16832052
  13. The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration.
    Sci Rep. 2012;2:488 PMID: 22761994
  14. Distinct signaling mechanisms regulate migration in unconfined versus confined spaces.
    J Cell Biol. 2013 Sep 2;202(5):807-24 PMID: 23979717
  15. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.
    Nat Cell Biol. 2014 Sep;16(9):909-17 PMID: 25150978
  16. Cell migration: a physically integrated molecular process.
    Cell. 1996 Feb 9;84(3):359-69 PMID: 8608589
  17. Water permeation drives tumor cell migration in confined microenvironments.
    Cell. 2014 Apr 24;157(3):611-23 PMID: 24726433
  18. A distinctive role for focal adhesion proteins in three-dimensional cell motility.
    Nat Cell Biol. 2010 Jun;12(6):598-604 PMID: 20473295
  19. Cells assemble invadopodia-like structures and invade into matrigel in a matrix metalloprotease dependent manner in the circular invasion assay.
    PLoS One. 2012;7(2):e30605 PMID: 22347388
  20. Focal adhesion size uniquely predicts cell migration.
    FASEB J. 2013 Apr;27(4):1351-61 PMID: 23254340
  21. Three-dimensional cell migration does not follow a random walk.
    Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):3949-54 PMID: 24594603
  22. Analysis of the roles of microvessel endothelial cell random motility and chemotaxis in angiogenesis.
    J Theor Biol. 1991 Oct 7;152(3):377-403 PMID: 1721100
  23. Stochastic model of leukocyte chemosensory movement.
    J Math Biol. 1987;25(3):229-62 PMID: 3625051
  24. Immune cell migration in inflammation: present and future therapeutic targets.
    Nat Immunol. 2005 Dec;6(12):1182-90 PMID: 16369557
  25. Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners.
    Nat Commun. 2012 Mar 06;3:719 PMID: 22395610
  26. Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells.
    Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):E384-93 PMID: 24324133
  27. Quantification of human neutrophil motility in three-dimensional collagen gels. Effect of collagen concentration.
    Biophys J. 1992 Feb;61(2):306-15 PMID: 1547321
  28. New dimensions in cell migration.
    Nat Rev Mol Cell Biol. 2012 Nov;13(11):743-7 PMID: 23072889
  29. A Rac switch regulates random versus directionally persistent cell migration.
    J Cell Biol. 2005 Aug 29;170(5):793-802 PMID: 16129786
  30. Cell migration: integrating signals from front to back.
    Science. 2003 Dec 5;302(5651):1704-9 PMID: 14657486
  31. High-throughput ballistic injection nanorheology to measure cell mechanics.
    Nat Protoc. 2012 Jan 05;7(1):155-70 PMID: 22222790
  32. Wound healing--aiming for perfect skin regeneration.
    Science. 1997 Apr 4;276(5309):75-81 PMID: 9082989
  33. Functional analysis of spontaneous cell movement under different physiological conditions.
    PLoS One. 2008 Jul 09;3(7):e2648 PMID: 18612377
Article Info
Journal
Nature protocols
Abbr.
Nat Protoc
ISSN
1750-2799
Published
2015-03-00
Epub
2015-00-26
Pages
517-27
Language
English
Region
England
NLM ID
101284307
PMCID
PMC4911638
Subset
IM
Grants
NCI NIH HHS · R01 CA174388 · United States
NCI NIH HHS · U54CA143868 · United States
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