420회 Distinct patterns of Fibroblast Spreading, Migration, and Aggrega…

420회 (2008. 11. 6.)

연사: 이 상 명, 중앙대학교 생명과학과

제목: Distinct Patterns of Fibroblast Spreading, Migration, and Aggregation in the Four Quadrants of Cell Mechanics  

Abstract 

Recently we described the four quadrants of fibroblast mechanics: Intersection of promigratory and procontractile growth factor environments with high tension and low tension cell-matrix interactions. In the current studies, we compare human fibroblast spreading, migration and aggregation in the four quadrants. Under promigratory conditions (PDGF-containing medium), fibroblasts developed dendritic extensions without actin stress fibers on "soft" 1.5 mg/ml collagen matrices (low cell-matrix tension state) and lamellar extensions with stress fibers on "hard"4.0 mg/ml collagen matrices or collagen coverslips (high cell-matrix tension). Under procontractile conditions (serum-containing medium), cells interacting with 1.5 mg/ml collagen matrices tended to remain in the retractedstate and were delayed in spreading. Cell migration was greatest for fibroblasts under promigratory conditions (+PDGF) at a high tension state and lowest for cells under procontractile conditions (+serum) at a high tension state. Myosin IIA was selectively required for cell migration under the promigratory/high tension state and procontractile/low tension state conditions. Fibroblast aggregation occurred under procontractile conditions (+serum) and low tension state but not otherwise. If aggregates were pre-formed, then switching the cells to promigratory conditions (+PDGF) resulted in their disruption. Human fibroblasts expressing H-Ras (which show decreased cell-cell interactions) did not form cell aggregates under any conditions. These findings demonstrate that in the four quadrants of cell mechanics, fibroblasts exhibit a high degree of plasticity not previously appreciated. We suggest that cell spreading, migration and aggregation are regulated by the balance between cell protrusion (promigratory conditions), retraction (procontractile conditions), and adhesion (cell-matrix tension state and cell-cell adhesion). Most research on fibroblasts has been carried out in the pro-contractile/high tension environment of cells on glass or plastic cover slips in serum-containing medium. Signaling mechanisms and regulatory networks that control cell mechanics likely will be utilized differently in the different quadrants.