Effects of morphological patterning on endothelial cell migration.

The migration of vascular endothelial cells (ECs) plays an important role in vascular remodeling. Here we studied the effects of cell morphology on the migration of bovine aortic ECs by culturing cells on micropatterned strips of collagen matrix (60-, 30-, and 15-microm wide). The spreading areas of the cells on 15- and 30-microm wide strips were 30% lower than those on 60-microm wide strips and unpatterned collagen. The cells on 15-microm wide strips completely aligned in the direction of the strip, and had significantly lower shape index than those in all other groups. On strips of all widths, ECs tended to migrate in the direction of strips. ECs on 15-microm wide strips had highest speed, particularly in the direction of the strip. Vinculin staining showed that the leading edge of ECs on 15-microm wide strips had focal adhesions that were oriented with their lamellipodial protrusion and the direction of cell migration; this arrangement of the focal adhesions may promote EC migration. The present study provides direct evidence on the role of cell morphology in EC migration, and will help us to understand the mechanisms of EC migration during angiogenesis and wound healing.

[1]  R M Nerem,et al.  Vascular endothelial morphology as an indicator of the pattern of blood flow. , 1981, Journal of biomechanical engineering.

[2]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[3]  Milan Mrksich,et al.  Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates , 1999, In Vitro Cellular & Developmental Biology - Animal.

[4]  Sean P. Palecek,et al.  Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness , 1997, Nature.

[5]  M. Sheetz,et al.  Cell migration: regulation of force on extracellular-matrix-integrin complexes. , 1998, Trends in cell biology.

[6]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[7]  M. Bissell,et al.  The Influence of Extracellular Matrix on Gene Expression: Is Structure the Message? , 1987, Journal of Cell Science.

[8]  C F Dewey,et al.  The dynamic response of vascular endothelial cells to fluid shear stress. , 1981, Journal of biomechanical engineering.

[9]  W. K. Tucker,et al.  Endothelial Nuclear Patterns in the Canine Arterial Tree with Particular Reference to Hemodynamic Events , 1972, Circulation research.

[10]  M. Toner,et al.  Cellular Micropatterns on Biocompatible Materials , 1998, Biotechnology progress.

[11]  B. Chen,et al.  Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. , 1999, The Journal of clinical investigation.

[12]  Anne J. Ridley,et al.  The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors , 1992 .

[13]  Donald E. Ingber,et al.  The structural and mechanical complexity of cell-growth control , 1999, Nature Cell Biology.