Cellular and Molecular Life Sciences CMLS

, Volume 57, Issue 1, pp 41–64

The biology of cell locomotion within three-dimensional extracellular matrix

  • P. Friedl
  • E.-B. Bröcker

DOI: 10.1007/s000180050498

Cite this article as:
Friedl, P. & Bröcker, EB. CMLS, Cell. Mol. Life Sci. (2000) 57: 41. doi:10.1007/s000180050498

Abstract.

Cell migration in three-dimensional (3-D) extracellular matrix (ECM) is not a uniform event but rather comprises a modular spectrum of interdependent biophysical and biochemical cell functions. Haptokinetic cell migration across two-dimensional (2-D) surfaces consists of at least three processes: (i) the protrusion of the leading edge for adhesive cell-substratum interactions is followed by (ii) contraction of the cell body and (iii) detachment of the trailing edge. In cells of flattened morphology migrating slowly across 2-D substrate, contact-dependent clustering of adhesion receptors including integrins results in focal contact and stress fiber formation. While haptokinetic migration is predominantly a function of adhesion and deadhesion events lacking spatial barriers towards the advancing cell body, the biophysics of the tissues require a set of cellular strategies to overcome matrix resistance. Matrix barriers force the cells to adapt their morphology and change shape and/or enzymatically degrade ECM components, either by contact-dependent proteolysis or by protease secretion. In 3-D ECM, in contrast to 2-D substrate, the cell shape is mostly bipolar and the cytoskeletal organization is less stringent, frequently lacking discrete focal contacts and stress fibers. Morphologically large spindle-shaped cells (i.e., fibroblasts, endothelial cells, and many tumor cells) of high integrin expression and strong cytoskeletal contractility utilize integrin-dependent migration strategies that are coupled to the capacity to reorganize ECM. In contrast, a more dynamic ameboid migration type employed by smaller cells expressing low levels of integrins (i.e., T lymphocytes, dendritic cells, some tumor cells) is characterized by largely integrin-independent interaction strategies and flexible morphological adaptation to preformed fiber strands, without structurally changing matrix architecture. In tumor invasion and angiogenesis, migration mechanisms further comprise the migration of entire cell clusters or strands maintaining stringent cell-cell adhesion and communication while migrating. Lastly, cellular interactions, enzyme and cytokine secretion, and tissue remodeling provided by reactive stroma cells i.e. fibroblasts and macrophage contribute to cell migration. In conclusion, depending on the cellular composition and tissue context of migration, diverse cellular and molecular migration strategies can be developed by different cell types.

Key words. Collagen matrix; cell migration; integrins; CD44; matrix metalloproteinases; attachment; detachment; tissue remodeling; tumor invasion; antibody blocking; haptokinetic. 

Copyright information

© Birkhäuser Verlag Basel, 2000

Authors and Affiliations

  • P. Friedl
    • 1
  • E.-B. Bröcker
    • 1
  1. 1.Cell Migration Laboratory, Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg (Germany), Fax +49 031 2012700, e-mail: peter.fr@mail.uni-wuerzburg.deDE