Skip to main content
SpringerLink
Log in

Dynamic imaging of cellular interactions with extracellular matrix

  • Histochemistry and Cell Biology Lecture
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Adhesive and proteolytic interactions of cells with components of the extracellular matrix (ECM) are fundamental to morphogenesis, tissue assembly and remodeling, and cell migration as well as signal acquisition from tissue-bound factors. The visualization from fixed samples provides snapshot-like, static information on the cellular and molecular dynamics of adhesion receptor and protease functions toward ECM, such as interstitial fibrillar tissues and basement membranes. Recent technological developments additionally support the dynamic imaging of ECM scaffolds and the interaction behavior of cells contained therein. These include differential interference contrast, confocal reflection microscopy, optical coherence tomography, and multiphoton microscopy and second-harmonic generation imaging. Most of these approaches are combined with fluorescence imaging using derivates of GFP and/or other fluorescent dyes. Dynamic 3D imaging has revealed an unexpected degree of dynamics and turnover of cell adhesion and migration as well as basic mechanisms that lead to proteolytic remodeling of connective tissue by stromal cells and invading tumor cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–D
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aletta JM, Greene LA (1988) Growth cone configuration and advance: a time-lapse study using video-enhanced differential interference contrast microscopy. J Neurosci 8:1425–1435

    CAS  PubMed  Google Scholar 

  • Barton JK, Gossage KW, Xu W, Ranger-Moore JR, Saboda K, Brooks CA, Duckett LD, Salasche SJ, Warneke JA, Alberts DS (2003) Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study. Technol Cancer Res Treat 2:525–535

    CAS  PubMed  Google Scholar 

  • Boyde A, Jones SJ (1995) Mapping and measuring surfaces using reflection confocal microscopy. In: Pawley JB (ed) Handbook of biological confocal microscopy. Plenum, New York, pp 255–265

  • Brightman AO, Rajwa BP, Sturgis JE, McCallister ME, Robinson JP, Voytik-Harbin SL (2000) Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. Biopolymers 54:222–234

    Article  CAS  PubMed  Google Scholar 

  • Campagnola PJ, Loew LM (2003) Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol 21:1356–1360

    Article  CAS  PubMed  Google Scholar 

  • Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, Mohler WA (2002) Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys J 82:493–508

    CAS  PubMed  Google Scholar 

  • Cheng PC, Kriete A (1995) Image contrast in confocal light microscopy. In: Pawley JB (ed) Handbook of biological confocal microscopy. Plenum, New York, pp 281–310

  • Cukierman E, Pankov R, Stevens DR, Yamada KM (2001) Taking cell-matrix adhesions to the third dimension. Science 294:1708–1712

    Article  CAS  PubMed  Google Scholar 

  • Davies PF, Robotewskyj A, Griem ML (1993) Endothelial cell adhesion in real time. Measurements in vitro by tandem scanning confocal image analysis. J Clin Invest 91:2640–2652

    CAS  PubMed  Google Scholar 

  • Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76

    CAS  PubMed  Google Scholar 

  • Dickinson ME, Simbuerger E, Zimmermann B, Waters CW, Fraser SE (2003) Multiphoton excitation spectra in biological samples. J Biomed Opt 8:329–338

    Article  PubMed  Google Scholar 

  • Dombeck DA, Kasischke KA, Vishwasrao HD, Ingelsson M, Hyman BT, Webb WW (2003) Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy. Proc Natl Acad Sci U S A 100:7081–7086

    Article  CAS  PubMed  Google Scholar 

  • Friedl P (2004a) Dynamic imaging of the immune system. Curr Opin Immunol 16:389–393

    Article  Google Scholar 

  • Friedl P (2004b) Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16:14–23

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Brocker EB (2004) Reconstructing leukocyte migration in 3D extracellular matrix by time-lapse videomicroscopy and computer-assisted tracking. Methods Mol Biol 239:77–90

    PubMed  Google Scholar 

  • Friedl P, Wolf K (2003a) Proteolytic and non-proteolytic migration of tumour cells and leucocytes. Biochem Soc Symp 70:277–285

    CAS  PubMed  Google Scholar 

  • Friedl P, Wolf K (2003b) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Maaser K, Klein CE, Niggemann B, Krohne G, Zanker KS (1997) 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 57:2061–2070

    CAS  PubMed  Google Scholar 

  • Friedl P, Entschladen F, Conrad C, Niggemann B, Zanker KS (1998a) CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion. Eur J Immunol 28:2331–2343

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Zanker KS, Brocker EB (1998b) Cell migration strategies in 3-D extracellular matrix: differences in morphology, cell matrix interactions, and integrin function. Microsc Res Tech 43:369–378

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Borgmann S, Brocker EB (2001) Amoeboid leukocyte crawling through extracellular matrix: lessons from the Dictyostelium paradigm of cell movement. J Leukoc Biol 70:491–509

    CAS  PubMed  Google Scholar 

  • Friedl P, Hegerfeldt Y, Tusch M (2004) Collective cell migration in morphogenesis and cancer. Eur J Dev Biol (in press)

  • Fukuchi T, Takahashi K, Uyama M, Matsumura M (2001) Comparative study of experimental choroidal neovascularization by optical coherence tomography and histopathology. Jpn J Ophthalmol 45:252–258

    Article  CAS  PubMed  Google Scholar 

  • Gladkova ND, Petrova GA, Nikulin NK, Radenska-Lopovok SG, Snopova LB, Chumakov YP, Nasonova VA, Gelikonov VM, Gelikonov GV, Kuranov RV, Sergeev AM, Feldchtein FI (2000) In vivo optical coherence tomography imaging of human skin: norm and pathology. Skin Res Technol 6:6–16

    Article  PubMed  Google Scholar 

  • Hegerfeldt Y, Tusch M, Brocker EB, Friedl P (2002) Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, beta1-integrin function, and migration strategies. Cancer Res 62:2125–2130

    CAS  PubMed  Google Scholar 

  • Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, et al (1991) Optical coherence tomography. Science 254:1178–1181

    CAS  PubMed  Google Scholar 

  • Keith CH, Bird GJ, Farmer MA (1998) Coherent backscatter enhances reflection confocal microscopy. Biotechniques 25:858–866

    CAS  PubMed  Google Scholar 

  • Konig K (2000) Multiphoton microscopy in life sciences. J Microsc 200:83–104

    Article  CAS  PubMed  Google Scholar 

  • Konig K, Riemann I (2003) High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. J Biomed Opt 8:432–439

    Article  PubMed  Google Scholar 

  • Korff T, Augustin HG (1999) Tensional forces in fibrillar extracellular matrices control directional capillary sprouting. J Cell Sci 112:3249–3258

    CAS  PubMed  Google Scholar 

  • Lippincott-Schwartz J, Altan-Bonnet N, Patterson GH (2003) Photobleaching and photoactivation: following protein dynamics in living cells. Nat Cell Biol 5(suppl):S7–S14

    Article  Google Scholar 

  • Maaser K, Wolf K, Klein CE, Niggemann B, Zanker KS, Brocker EB, Friedl P (1999) 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 10:3067–3079

    CAS  PubMed  Google Scholar 

  • Mempel TR, Henrickson SE, Von Andrian UH (2004a) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154–159

    Article  CAS  PubMed  Google Scholar 

  • Mempel TR, Scimone ML, Mora JR, von Andrian UH (2004b) In vivo imaging of leukocyte trafficking in blood vessels and tissues. Curr Opin Immunol 16:406–417

    Article  Google Scholar 

  • Miller MJ, Wei SH, Parker I, Cahalan MD (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296:1869–1873

    Article  CAS  PubMed  Google Scholar 

  • Niewöhner J, Weber I, Maniak M, Müller-Tauchenberger A, Gerisch G (1997) Talin-null cells from Dictyostelium are strongly defective in adhesion to particle and substrate surfaces and slightly impaired in cytokinesis. J Cell Biol 138:349–361

    Article  PubMed  Google Scholar 

  • Petroll WM, Ma L (2003) Direct, dynamic assessment of cell-matrix interactions inside fibrillar collagen lattices. Cell Motil Cytoskeleton 55:254–264

    Article  PubMed  Google Scholar 

  • Petroll WM, Cavanagh HD, Jester JV (2004) Dynamic three-dimensional visualization of collagen matrix remodeling and cytoskeletal organization in living corneal fibroblasts. Scanning 26:1–10

    PubMed  Google Scholar 

  • Ploem JS (1975) Reflection-contrast microscopy as a tool for investigation of the attachment of living cells to a glass surface. In: van Furth R (ed) Handbook of biological confocal microscopy. Blackwell, Oxford, pp 404–421

  • Rieckhoff KE, Peticolas WL (1965) Optical second-harmonic generation in crystalline amino acids. Science 147:610–611

    CAS  PubMed  Google Scholar 

  • Rosso F, Giordano A, Barbarisi M, Barbarisi A (2004) From cell-ECM interactions to tissue engineering. J Cell Physiol 199:174–180

    Article  CAS  PubMed  Google Scholar 

  • Seftor RE, Seftor EA, Koshikawa N, Meltzer PS, Gardner LM, Bilban M, Stetler-Stevenson WG, Quaranta V, Hendrix MJ (2001) Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 61:6322–6327

    CAS  PubMed  Google Scholar 

  • Simian M, Hirai Y, Navre M, Werb Z, Lochter A, Bissell MJ (2001) The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 128:3117–3131

    CAS  PubMed  Google Scholar 

  • Tamariz E, Grinnell F (2002) Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol Biol Cell 13:3915–3929

    Article  CAS  PubMed  Google Scholar 

  • Vanni S, Lagerholm BC, Otey C, Taylor DL, Lanni F (2003) Internet-based image analysis quantifies contractile behavior of individual fibroblasts inside model tissue. Biophys J 84:2715–2727

    CAS  PubMed  Google Scholar 

  • Voytik-Harbin SL, Roeder BA, Sturgis JE, Kokini K, Robinson JP (2003) Simultaneous mechanical loading and confocal reflection microscopy for three-dimensional microbiomechanical analysis of biomaterials and tissue constructs. Microsc Microanal 9:74–85

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Wyckoff JB, Frohlich VC, Oleynikov Y, Huttelmaier S, Zavadil J, Cermak L, Bottinger EP, Singer RH, White JG, Segall JE, Condeelis JS (2002) Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res 62:6278–6288

    CAS  PubMed  Google Scholar 

  • Webb DJ, Brown CM, Horwitz AF (2003) Illuminating adhesion complexes in migrating cells: moving toward a bright future. Curr Opin Cell Biol 15:614–620

    Article  CAS  PubMed  Google Scholar 

  • Wolf K, Mazo I, Leung H, Engelke K, von Andrian UH, Deryugina EI, Strongin AY, Brocker EB, Friedl P (2003a) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277

    Article  CAS  PubMed  Google Scholar 

  • Wolf K, Muller R, Borgmann S, Brocker EB, Friedl P (2003b) Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 102:3262–3269

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Whiteman S, van Pittius DG, He Y, Wang RK, Spiteri MA (2004) Use of optical coherence tomography in delineating airways microstructure: comparison of OCT images to histopathological sections. Phys Med Biol 49:1247–1255

    Article  PubMed  Google Scholar 

  • Yeh AT, Choi B, Nelson JS, Tromberg BJ (2003) Reversible dissociation of collagen in tissues. J Invest Dermatol 121:1332–1335

    CAS  PubMed  Google Scholar 

  • Yeh AT, Kao B, Jung WG, Chen Z, Nelson JS, Tromberg BJ (2004) Imaging wound healing using optical coherence tomography and multiphoton microscopy in an in vitro skin-equivalent tissue model. J Biomed Opt 9:248–253

    Article  PubMed  Google Scholar 

  • Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW (2003) Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci U S A 100:7075–7080

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Center for Interdisciplinary Research (IZKF) Würzburg, grant number D/21-(1). I gratefully acknowledge Hongqi Lü and Katarina Wolf for expert assistance with confocal microscopy. I am grateful to Dorothee Schroth, Leica Microsystems, Mannheim, Germany, for expert technical support with multiphoton microscopy.

Author information

Authors and Affiliations

  1. Rudolf-Virchow Center, DFG Research Center for Experimental Biomedicine, and Department of Dermatology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany

    Peter Friedl

Authors
  1. Peter Friedl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Friedl.

Additional information

The Histochemistry and Cell Biology Lecture presented at the 12th International Congress of Histochemistry and Cytochemistry in La Jolla, California, USA, 24–28 July 2004

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friedl, P. Dynamic imaging of cellular interactions with extracellular matrix. Histochem Cell Biol 122, 183–190 (2004). https://doi.org/10.1007/s00418-004-0682-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-004-0682-0

Keywords

Search

Navigation