Research Interests

Research in my laboratory concerns regulation of cell migration and proliferation by the interaction of growth factors and extracellular matrix. Migration of fibroblasts in three dimensional collagen matrix cultures results in matrix remodeling and contraction. The process is adaptive and progressive. Molecular signaling and motor mechanisms that regulate contraction vary according to local matrix organization, and cells switch between proliferative and quiescent states depending upon isometric tension.

Tissues and organs are three dimensional structures, and extracellular matrix plays a key role in their organization in vivo. We study this organizational function using three dimensional cultures because they introduce complex patterns of dynamic, cell-extracellular matrix interactions not observable in routine cell culture. Above all, this means on one hand that cells will be completely surrounded by extracellular matrix; and on the other, that cells will be able to remodel the matrix thereby changing matrix properties and, in reciprocal fashion, cell features will then change as well.

In addition to its general importance for understanding cell function and structure, studies on cell biology in three dimensions are important to the emergent field of tissue engineering, one of whose goals is to produce biomemetic materials for artificial tissues and organs. Moreover, fibroblast remodeling of three dimensional collagen matrices provides a useful in vitro model of wound repair.

Recent Publications

Grinnell, F. (2003) Fibroblast biology in three-dimensional collagen matrices. Trends in Cell Biology. 13: 264-269.

Jiang, H. and Grinnell, F. (2005) Cell-matrix entanglement and mechanical anchorage of fibroblasts in three dimensional collagen matrices. Molecular Biology of the Cell. 16: 5070-6

Grinnell, F., Rocha, L. B., Iucu, C., Rhee, S. and Jiang, H. (2006) Nested collagen matrices: A new model to study migration of human fibroblast populations in three dimensions. Exp Cell Res. 312: 86–94

Rhee, S. and Grinnell, F. (2006) p21-activated kinase 1: Convergence point in PDGF and LPA-stimulated collagen matrix contraction by human fibroblasts. J. Cell Biol. 172: 423-432.

Rhee, S., Jiang, H., Ho, C.H., and Grinnell, F. (2007) Microtubule function in fibroblast spreading is modulated according to the tension state of cell-matrix interactions. Proc. Nat. Acad. Sci. USA. 104: 5425-5430

Rhee, S. and Grinnell, F (2007) Fibroblast mechanics in 3D collagen matrices. Advance Drug Delivery Reviews. 59: 1299-1305

Jiang, H., Rhee, S., Ho, C.H. and Grinnell, F. (2008) Distinguishing fibroblast promigratory and procontractile growth factor environments in 3D collagen matrices. FASEB J. 22: 2151-2160.

Miron-Mendoza, M., Seemann, J. and Grinnell, F. (2008) Collagen fibril flow and tissue translocation coupled to fibroblast migration in 3D collagen matrices. Mol Biol. Cell. 19: 2051-8.

Other Selected Publications

Grinnell, F. and Hays, D. G. (1978) Induction of active cell spreading by substratum adsorbed ligands directed against the cell surface. Exp. Cell Res. 116: 275-284.

Grinnell, F. and Minter, D. (1978) Attachment and spreading of baby hamster kidney cells to collagen substrata. Proc. Natl. Acad. Sci. USA 75: 4408-4412.

Grinnell, F. (1978) Cellular adhesiveness and extracellular substrata. Int. Rev. Cytol. 53: 65-144.

Grinnell, F. and Feld, M. (1979) Initial adhesion of human fibroblasts in serum-free medium: Possible role of secreted fibronectin. Cell 17: 117-129.

Grinnell, F., Feld, M., and Minter, D. (1980) Cell adhesion to fibrinogen and fibrin substrata: Requirement for cold insoluble globulin. Cell 19: 517-525.

Grinnell, F. (1980) The fibroblast receptor for cell-substratum adhesion: Studies on the interaction of baby hamster kidney cells with latex beads coated by cold insoluble globulin (plasma fibronectin). J. Cell Biol. 86:104-112.

Grinnell, F., Billingham, R. E., and Burgess, L. (1981) Distribution of fibronectin during wound healing in vivo. J. Invest. Dermatol. 76: 181-189.

Grinnell, F. and Feld, M. (1981) Adsorption properties of fibronectin in relationship to biological activity. J. Biomed. Materials Res. 15: 363-381.

Grinnell, F. and Feld, M. (1982) Fibronectin adsorption on hydrophilic and hydrophobic surfaces detected by antibody binding and analyzed during cell adhesion in serum-containing medium. J. Biol. Chem. 257: 4888-4893.

Grinnell, F. (1984) Fibronectin and wound healing. J. Cell Biochem. 26:107-116.

Grinnell, F. and Lamke, Cheryl R. (1984) Reorganization of hydrated collagen lattices by human skin fibroblasts. J. Cell Science. 66: 51-63.

Guidry, C. and Grinnell, F. (1985) Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. J. Cell Sci. 79: 67-81.

Wysocki, A., Baxter, C.R., Bergstresser, P.R., Grinnell, F., Horowitz, M.S., and Horowitz, B. (1988) Topical fibronectin therapy for treatment of a patient with chronic stasis ulcers. Arch. Dermatol. 124: 175-177.

Grinnell, F., Fukazmizu, H., Pawelek, P., and Nakagawa, S. (1989) Collagen production, crosslinking, and fibril bundle assembly in matrix produced by fibroblasts in long term cultures supplemented with ascorbic acid. Exp. Cell Res. 181: 483-491.

Nakagawa, S., Pawalek, P., and Grinnell, F. (1989) Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness. Exp. Cell Res. 182: 572-582.

Fukamizu, H. and Grinnell, F. (1990) Spatial organization of extracellular matrix and fibroblast activity: Effects of serum, transforming growth factor-beta, and fibronectin. Exp. Cell Res. 190: 276-282.

Wysocki, A.B. and Grinnell, F. (1990) Fibronectin profiles in normal and chronic wound fluid. Lab. Investigation. 63:825-831.

Mochitate, K., Pawelek, P., and Grinnell, F. (1991) Stress-relaxation of contracted collagen gels: Disruption of the actin cytoskeleton, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. Exp. Cell Res. 193: 198-207.

Grinnell, F. (1992) Wound repair, keratinocyte activation, and integrin modulation. J. Cell Sci. 101: 1-5

Grinnell, F., Ho, C-H., and Wysocki, A. (1992) Degradation of fibronectin and vitronectin in wound fluid: Analysis by cell blotting, immunoblotting, and cell adhesion assays. J. Invest. Dermatol. 98: 410-416

Wysocki, A.B., Staiano-Coico, L., and Grinnell, F. (1993) Wound fluid from chronic ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J. Invest. Dermatol. 101: 64-68

Grinnell, F. (1994) Fibroblasts, myofibroblasts, and wound contraction. J. Cell Biol. 124: 401-404.

Grinnell, F. and Zhu, M. (1994) Identification of neutrophil elastase as the proteinase in burn wound fluid responsible for degradation of fibronectin. J. Invest. Dermatol. 103: 155-161.

Young, P. and Grinnell, F. (1994) Metalloproteinase activation cascade after burn injury: A longitudinal analysis of the human wound environment. J. Invest. Dermatol. 103: 660-664.

Grinnell, F. and Zhu, M (1996) Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin. J. Invest. Dermatol. 106: 335-341

Lin, Y-C., Ho, C-H., and Grinnell, F. (1997) Fibroblasts contracting collagen matrices form transient plasma membrane passages through which the cells take up FITC-dextran and Ca2+. Mol. Biol. Cell, 8: 59-71

Grinnell, F., Ho, C-H., Lin, Y-C., and Skuta, G. (1999) Differences in the regulation of fibroblast contraction of floating versus stressed collagen matrices. J. Biol. Chem. 274: 918-923.

Grinnell, F., Zhu, M., Carlson, M.A., Abrams, J.M. (1999) Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. Exp. Cell Res. 248: 608-619.

Grinnell, F. (2000) Fibroblast-collagen matrix contraction: Growth factor signalling and mechanical loading. Trends in Cell Biology. 10: 362-365.

Rosenfeldt, H. and Grinnell, F. (2000) Fibroblast quiescence and the disruption of ERK signaling in mechanically-unloaded collagen matrices. J. Biol. Chem. 275: 3088-3092.

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

Grinnell, F., Ho, C.H., Tamariz, E., Lee, D.J., and Skuta, G. (2003). Dendritic fibroblasts in three dimensional collagen matrices. Mol Biol Cell. 14: 384-395.

Abe, M., Ho, C.H., Kamm, K.E., and Grinnell, F. (2003) Different molecular motors mediate PDGF and LPA-stimulated floating collagen matrix contraction. J. Biol. Chem. 278: 47707-47712.