CoChat
Sign Up
Cited by 637Cellular Mechanics and InteractionsCollagen: Extraction and Characterization3D Printing in Biomedical Research

Collagen-based cell migration models in vitro and in vivo

Open access
Wolf, Katarina, Alexander, Stephanie, Schacht, Vivien, Coussens, Lisa M., von Andrian, Ulrich H., van Rheenen, Jacco, Deryugina, Elena, Friedl, Peter·2009·Seminars in Cell & Developmental Biology
DOI 10.1016/j.semcdb.2009.08.005PMC PMC4021709
Open this paper in CoChat — free account

Abstract

Fibrillar collagen is the most abundant extracellular matrix (ECM) constituent which maintains the structure of most interstitial tissues and organs, including skin, gut, and breast. Density and spatial alignments of the three-dimensional (3D) collagen architecture define mechanical tissue properties, i.e. stiffness and porosity, which guide or oppose cell migration and positioning in different contexts, such as morphogenesis, regeneration, immune response, and cancer progression. To reproduce interstitial cell movement in vitro with high in vivo fidelity, 3D collagen lattices are being reconstituted from extracted collagen monomers, resulting in the re-assembly of a fibrillar meshwork of defined porosity and stiffness. With a focus on tumor invasion studies, we here evaluate different in vitro collagen-based cell invasion models, employing either pepsinized or non-pepsinized collagen extracts, and compare their structure to connective tissue in vivo, including mouse dermis and mammary gland, chick chorioallantoic membrane (CAM), and human dermis. Using confocal reflection and two-photon-excited second harmonic generation (SHG) microscopy, we here show that, depending on the collagen source, in vitro models yield homogeneous fibrillar texture with a quite narrow range of pore size variation, whereas all in vivo scaffolds comprise a range from low- to high-density fibrillar networks and heterogeneous pore sizes within the same tissue. Future in-depth comparison of structure and physical properties between 3D ECM-based models in vitro and in vivo are mandatory to better understand the mechanisms and limits of interstitial cell movements in distinct tissue environments.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.semcdb.2009.08.005

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Collagen possesses properties suitable for anti-adhesion applications, including excellent biocompatibility, biodegradability, hydrophilicity, non-immunogenicity, and ability to act as a physical barrier against fibrin bridge formation.

    “Collagen possesses unique properties that make it highly suitable for anti-adhesion applications, including excellent biocompatibility, biodegradability, hydrophilicity, and non-immunogenicity, in addition to its ability to act as a physical barrier against fibrin bridge formation [20,21].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [21]

    The Introduction describes collagen as a mechanically stable tissue scaffold, and the Conclusions describe its fibre networks as barriers to cell movement. Neither section addresses anti-adhesion applications, the listed material properties, or prevention of fibrin bridge formation. Searches for those properties and for fibrin bridges found no relevant passage in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 68

  1. [1]Siegel RC Biosynthesis of collagen crosslinks: increased activity of purified lysyl oxidase with reconstituted collagen fibrils Proc Natl Acad Sci U S A 1974 71 4826 30 4531019 PMC433990
  2. [2]Sabeh F Shimizu-Hirota R Weiss SJ Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited J Cell Biol 2009 185 11 9 19332889 PMC2700505
  3. [3]Elbjeirami WM Yonter EO Starcher BC West JL Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity J Biomed Mater Res A 2003 66 513 21 12918034
  4. [4]Paszek MJ Zahir N Johnson KR Lakins JN Rozenberg GI Gefen A Tensional homeostasis and the malignant phenotype Cancer Cell 2005 8 241 54 16169468
  5. [5]Daley WP Peters SB Larsen M Extracellular matrix dynamics in development and regenerative medicine J Cell Sci 2008 121 255 64 18216330
  6. [6]Stetler-Stevenson WG Liotta LA Kleiner DE Jr Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis Faseb J 1993 7 1434 41 8262328
  7. [7]Zhai Y Hotary KB Nan B Bosch FX Munoz N Weiss SJ Expression of membrane type 1 matrix metalloproteinase is associated with cervical carcinoma progression and invasion Cancer Res 2005 65 6543 50 16061633
  8. [8]Harley BA Kim HD Zaman MH Yannas IV Lauffenburger DA Gibson LJ Microarchitecture of three-dimensional scaffolds influences cell migration behavior via junction interactions Biophys J 2008 95 4013 24 18621811 PMC2553126
  9. [9]Poole K Khairy K Friedrichs J Franz C Cisneros DA Howard J Molecular-scale topographic cues induce the orientation and directional movement of fibroblasts on two-dimensional collagen surfaces J Mol Biol 2005 349 380 6 15890202
  10. [10]Grew JC Ricci JL Alexander H Connective-tissue responses to defined biomaterial surfaces. II. Behavior of rat and mouse fibroblasts cultured on microgrooved substrates J Biomed Mater Res A 2008 85 326 35 17688289
  11. [11]Wolf K Wu YI Liu Y Geiger J Tam E Overall C Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion Nat Cell Biol 2007 9 893 904 17618273
  12. [12]Butcher DT Alliston T Weaver VM A tense situation: forcing tumour progression Nat Rev Cancer 2009 9 108 22 19165226 PMC2649117
  13. [13]Giannone G Sheetz MP Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways Trends Cell Biol 2006 16 213 23 16529933
  14. [14]Friedl P Wolf K Proteolytic and non-proteolytic migration of tumour cells and leucocytes Biochem Soc Symp 2003 277 85 14587300
  15. [15]Wolf K Muller R Borgmann S Brocker EB Friedl P Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases Blood 2003 102 3262 9 12855577
  16. [16]Doyle AD Wang FW Matsumoto K Yamada KM One-dimensional topography underlies three-dimensional fibrillar cell migration J Cell Biol 2009 184 481 90 19221195 PMC2654121
  17. [17]d’Ortho MP Stanton H Butler M Atkinson SJ Murphy G MT1-MMP on the cell surface causes focal degradation of gelatin films FEBS Lett 1998 421 159 64 9468298
  18. [18]Kim A Lakshman N Petroll WM Quantitative assessment of local collagen matrix remodeling in 3-D culture: the role of Rho kinase Exp Cell Res 2006 312 3683 92 16978606 PMC2075357
  19. [19]Friedl P Bröcker E-B The biology of cell locomotion within three-dimensional extracellular matrix Cell Mol Life Sci 2000 57 41 64 10949580 PMC11147156
  20. [20]Provenzano PP Eliceiri KW Campbell JM Inman DR White JG Keely PJ Collagen reorganization at the tumor-stromal interface facilitates local invasion BMC Med 2006 4 38 17190588 PMC1781458
  21. [21]Friedl P Maaser K Klein CE Niggemann B Krohne G Zanker KS Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44 Cancer Res 1997 57 2061 70 9158006
  22. [22]Campagnola PJ Millard AC Terasaki M Hoppe PE Malone CJ Mohler WA Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues Biophys J 2002 82 493 508 11751336 PMC1302489
  23. [23]Friedl P Wolf K Harms G von Andrian UH Biological second and third harmonic generation microscopy Curr Protoc Cell Biol 2007 Chapter 4 Unit 4 15 18228516
  24. [24]Bayan C Levitt JM Miller E Kaplan D Georgakoudi I Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels J Appl Physics 2009 105 102042-1 11 PMC3987166 24803683
  25. [25]Maaser K Wolf K Klein CE Niggemann B Zanker KS Brocker EB Functional hierarchy of simultaneously expressed adhesion receptors: integrin alpha2beta1 but not CD44 mediates MV3 melanoma cell migration and matrix reorganization within three-dimensional hyaluronan-containing collagen matrices Mol Biol Cell 1999 10 3067 79 10512851 PMC25559
  26. [26]Zipfel WR Williams RM Christie R Nikitin AY Hyman BT Webb WW Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation Proc Natl Acad Sci U S A 2003 100 7075 80 12756303 PMC165832
  27. [27]Wolf K Mazo I Leung H Engelke K von Andrian UH Deryugina EI Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis J Cell Biol 2003 160 267 77 12527751 PMC2172637
  28. [28]Andresen V Alexander S Heupel WM Hirschberg M Hoffman RM Friedl P Infrared multiphoton microscopy: subcellular-resolved deep tissue imaging Curr Opin Biotechnol 2009 20 54 62 19324541
  29. [29]Ntayi C Lorimier S Berthier-Vergnes O Hornebeck W Bernard P Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of melanoma cells within three-dimensional type I collagen lattices Exp Cell Res 2001 270 110 8 11597133
  30. [30]Carragher NO Walker SM Scott Carragher LA Harris F Sawyer TK Brunton VG Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function Oncogene 2006 25 5726 40 16652152
  31. [32]Sabeh F Ota I Holmbeck K Birkedal-Hansen H Soloway P Balbin M Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP J Cell Biol 2004 167 769 81 15557125 PMC2172570
  32. [33]Zijlstra A Lewis J Degryse B Stuhlmann H Quigley JP The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151 Cancer Cell 2008 13 221 34 18328426 PMC3068919
  33. [34]Alexander S Koehl GE Hirschberg M Geissler EK Friedl P Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model Histochem Cell Biol 2008 130 1147 54 18987875
  34. [35]Nelson CM Vanduijn MM Inman JL Fletcher DA Bissell MJ Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures Science 2006 314 298 300 17038622 PMC2933179
  35. [36]Kedrin D Gligorijevic B Wyckoff J Verkhusha VV Condeelis J Segall JE Intravital imaging of metastatic behavior through a mammary imaging window Nat Methods 2008 5 1019 21 18997781 PMC2820719
  36. [37]Gordley K Cole P Hicks J Hollier L A Comparative, long term assessment of soft tissue substitutes: AlloDerm, Enduragen, and Dermamatrix J Plast Reconstr Aesthet Surg 2009 19195956
  37. [38]Ehrmann RL Gey GO The growth of cells on a transparent gel of reconstituted rat-tail collagen J Natl Cancer Inst 1956 16 1375 403 13320119
  38. [39]Elsdale T Bard J Collagen substrata for studies on cell behavior J Cell Biol 1972 54 626 37 4339818 PMC2200288
  39. [40]Clark RA Lin F Greiling D An J Couchman JR Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan J Invest Dermatol 2004 122 266 77 15009704
  40. [41]Krause S Maffini MV Soto AM Sonnenschein C A novel 3D in vitro culture model to study stromal-epithelial interactions in the mammary gland Tissue Eng Part C Methods 2008 14 261 71 18694322
  41. [42]Deryugina EI Quigley JP Chapter 2. Chick embryo chorioallantoic membrane models to quantify angiogenesis induced by inflammatory and tumor cells or purified effector molecules Methods Enzymol 2008 444 21 41 19007659 PMC2699944
  42. [43]Mueller MM Fusenig NE Friends or foes - bipolar effects of the tumour stroma in cancer Nat Rev Cancer 2004 4 839 49 15516957
  43. [44]Helseth DL Jr Veis A Collagen self-assembly in vitro. Differentiating specific telopeptide-dependent interactions using selective enzyme modification and the addition of free amino telopeptide J Biol Chem 1981 256 7118 28 7251588
  44. [45]Friedl P Zanker KS Bröcker E-B Cell migration strategies in 3-D extracellular matrix: differences in morphology, cell matrix interactions, and integrin function Microsc Res Tech 1998 43 369 78 9858334
  45. [46]Wood S Jr Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber AMA Arch Pathol 1958 66 550 68 13582395
  46. [47]Cliff WJ The acute inflammatory reaction in the rabbit ear chamber with particular reference to the phenomenon of leukocytic migration J Exp Med 1966 124 543 56 5922284 PMC2138248
  47. [48]Baez S An open cremaster muscle preparation for the study of blood vessels by in vivo microscopy Microvasc Res 1973 5 384 94 4709735
  48. [49]Mempel TR Moser C Hutter J Kuebler WM Krombach F Visualization of leukocyte transendothelial and interstitial migration using reflected light oblique transillumination in intravital video microscopy J Vasc Res 2003 40 435 41 14530600
  49. [50]Mazo IB Gutierrez-Ramos JC Frenette PS Hynes RO Wagner DD von Andrian UH Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1 J Exp Med 1998 188 465 74 9687524 PMC2212463
  50. [51]Endrich B Asaishi K Gotz A Messmer K Technical report--a new chamber technique for microvascular studies in unanesthetized hamsters Res Exp Med (Berl) 1980 177 125 34 7003665
  51. [52]Asaishi K Endrich B Gotz A Messmer K Quantitative analysis of microvascular structure and function in the amelanotic melanoma A-Mel-3 Cancer Res 1981 41 1898 904 7214358
  52. [53]Armstrong PB Quigley JP Sidebottom E Transepithelial invasion and intramesenchymal infiltration of the chick embryo chorioallantois by tumor cell lines Cancer Res 1982 42 1826 37 7066899
  53. [54]Condeelis J Segall JE Intravital imaging of cell movement in tumours Nat Rev Cancer 2003 3 921 30 14737122
  54. [55]Pinner S Sahai E Imaging amoeboid cancer cell motility in vivo J Microsc 2008 231 441 5 18754999
  55. [56]Sidani M Wyckoff J Xue C Segall JE Condeelis J Probing the microenvironment of mammary tumors using multiphoton microscopy J Mammary Gland Biol Neoplasia 2006 11 151 63 17106644
  56. [57]Wakelin MW Sanz MJ Dewar A Albelda SM Larkin SW Boughton-Smith N An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane J Exp Med 1996 184 229 39 8691137 PMC2192663
  57. [58]Gligorijevic B Kedrin D Segall JE Condeelis J van Rheenen J Dendra2 photoswitching through the Mammary Imaging Window J Vis Exp 2009 28 PMC2794883 19578330
  58. [59]Deryugina EI Quigley JP Chick embryo chorioallantoic membrane model systems to study and visualize human tumor cell metastasis Histochem Cell Biol 2008 130 1119 30 19005674 PMC2699943
  59. [60]Li XY Ota I Yana I Sabeh F Weiss SJ Molecular dissection of the structural machinery underlying the tissue-invasive activity of membrane type-1 matrix metalloproteinase Mol Biol Cell 2008 19 3221 33 18495869 PMC2488283
  60. [61]van Kilsdonk JW Wilting RH Bergers M van Muijen GN Schalkwijk J van Kempen LC Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule Cancer Res 2008 68 3671 9 18483249
  61. [62]Brown E McKee T diTomaso E Pluen A Seed B Boucher Y Jain RK Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation Nat Med 2003 9 796 800 12754503
  62. [63]Han X Burke RM Zettel ML Tang P Brown EB Second harmonic properties of tumor collagen: determining the structural relationship between reactive stroma and healthy stroma Opt Express 2008 16 1846 59 18542263
  63. [64]Bell SE Mavila A Salazar R Bayless KJ Kanagala S Maxwell SA Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling J Cell Sci 2001 114 2755 73 11683410
  64. [65]Friedl P Wolf K Proteolytic interstitial cell migration: a five-step process Cancer Metastasis Rev 2009 28 129 35 19153672
  65. [66]Maniotis AJ Folberg R Hess A Seftor EA Gardner LM Pe’er J Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry Am J Pathol 1999 155 739 52 10487832 PMC1866899
  66. [67]Raub CB Unruh J Suresh V Krasieva T Lindmo T Gratton E Image correlation spectroscopy of multiphoton images correlates with collagen mechanical properties Biophys J 2008 94 2361 73 18065452 PMC2257909
  67. [68]Raub CB Suresh V Krasieva T Lyubovitsky J Mih JD Putnam AJ Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy Biophys J 2007 92 2212 22 17172303 PMC1861799
  68. [69]Gobeaux F Mosser G Anglo A Panine P Davidson P Giraud-Guille MM Fibrillogenesis in dense collagen solutions: a physicochemical study J Mol Biol 2008 376 1509 22 18234220

Cited by

Sorted by citations

Authors
Wolf, K., Alexander, S., Schacht, V., Coussens, L. M., von Andrian, U. H., van Rheenen, J., Deryugina, E., & Friedl, P.
Affiliations
  • Radboud University Nijmegen (NL)
  • University of Würzburg (DE)
  • Harvard University (US)
  • University of California, San Francisco (US)
  • Scripps Research Institute (US)
Corresponding author
Wolf, Katarina
ORCID
Venue
Seminars in Cell & Developmental Biology
Publisher
Elsevier BV
Published
2009-10
Volume
20
Issue
8
Pages
931-941
ISSN
1084-9521 (ISSN-L)
DOI
10.1016/j.semcdb.2009.08.005
PMC
PMC4021709
OpenAlex
W2172240370
Cited by
637
References
1
Citations by year
2026: 19 · 2025: 33 · 2024: 34 · 2023: 33 · 2022: 36 · 2021: 42 · 2020: 54 · 2019: 43 · 2018: 56 · 2017: 37 · 2016: 42 · 2015: 32 · 2014: 46 · 2013: 36 · 2012: 37
FWCI
2.35
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Cell and Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • National Cancer Institute (R01CA098075, CA 098075)
  • National Institute of Allergy and Infectious Diseases (R01AI072252, R01AI069259)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
collagen, extracellular matrix, cell migration, tumor invasion, tissue stiffness, in vitro model, chick chorioallantoic membrane, dermis, mammary gland
MeSH terms
Animals, Cell Movement, Collagen, Extracellular Matrix, Humans, Models, Biological, Neoplasms

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review