Cell migration strategies in 3-D extracellular matrix: Differences in morphology, cell matrix interactions, and integrin function
✍ Scribed by Friedl, Peter; Zänker, Kurt S.; Bröcker, Eva-B.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 545 KB
- Volume
- 43
- Category
- Article
- ISSN
- 1059-910X
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✦ Synopsis
Cell migration in extracellular matrix is a complex process of adhesion and deadhesion events combined with cellular strategies to overcome the biophysical resistance imposed by three-dimensionally interconnected matrix ligands. Using a 3-D collagen matrix migration model in combination with computer-assisted cell tracking for reconstruction of migration paths and confocal microscopy, we investigated molecular principles governing cell-matrix interactions and migration of different cell types. Highly invasive MV3 melanoma cells and fibroblasts are large and highly polarized cells migrating at low speed (0.1-0.5 µm/min) and at high directional persistence. MV3 melanoma cells utilize adhesive migration strategies as characterized by high 1 integrin surface expression, 1 integrin clustering at interactions with matrix fibers, and 1 integrinmediated adhesion for force generation and migration. In contrast, T lymphocytes and dendritic cells are highly mobile cells of lower 1 integrin expression migrating at 10-to 40-fold higher velocities, and directionally unpredictable path profiles. This migration occurs in the absence of focal adhesions and largely independent of 1 integrin-mediated adhesion. Whereas cell-matrix interactions of migrating tumor cells result in traction and reorientation of collagen fibers, partial matrix degradation, and pore formation, leukocytes form transient and short-lived interactions with the collagen lacking structural proteolysis and matrix remodeling. In conclusion, the 3-D extracellular matrix provides a spatially complex and biomechanically demanding substrate for cell migration, thereby differing from cell migration across planar ligands. Highly adhesive and integrin-dependent migration strategies detected in morphologically large and slowly migrating cells may result in reorganization of the extracellular matrix, whereas leukocytes favor largely integrin-independent, rapid, and flexible migration strategies lacking typical focal adhesions and structural matrix remodeling.