Fibrous connective tissues provide mechanical
support and frameworks for the other tissues of the body and play an integral
role in normal tissue physiology and pathology. We use fibroblasts interacting
with three dimensional collagen as a model system of fibrous connective
tissue to learn about cell behavior in a tissue-like environment. Our
research focuses on motile and mechanical interactions between fibroblasts
and collagen matrices, analyzing these interactions at global and subcellular
levels to identify unique features of mechanical feedback between cells
and the matrix, and the impact of the cell-matrix tension state on cell
morphology and mechanical behavior. Our studies are important for understanding
features of tissue fibrosis in relationship to wound repair, tumorigenesis
and aging and for development of biomemetic materials to produce artificial
tissues and organs as part of the emerging field of tissue engineering.
da Rocha-Azevedo, B., Ho, C.H., and Grinnell, F. (2013) Fibroblast cluster formation on 3D collagen matrices requires cell contraction dependent fibronectin matrix organization. Exp Cell Res. 319: 546-555.
Han B, Teo KY, Ghosh, S., Dutton, J.C., and Grinnell, F. (2013) Thermomechanical analysis of freezing-induced cell-fluid-matrix interactions in engineered tissues. J Mech Behav Biomed Mater. 18: 67-80.
Velasquez, L.S., Sutherland, L.B., Liu, Z., Grinnell, F., Kamm, K.E., Schneider, J.W., Olson, E.N., Small, E.M. (2013) Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing. Proc Natl Acad Sci USA. 110:16850-16855.
Liu Z, Ho CH, Grinnell
F., (2014) The different roles of myosin IIA and myosin IIB in contraction
of 3D collagen matrices by human fibroblasts. Exp Cell Res. 326:295-306
Park, S., Seawright,
A., Park, S., Dutton, J.C., Grinnell, F., and Han, B. (2015) Preservation
of tissue microstructure and functionality during freezing by modulation
of cytoskeletal structure. J Mech Behav Biomed Mater. Jan 24;45C:32-44.
Grinnell, F. (1978) Cellular adhesiveness and extracellular substrata. Int. Rev. Cytol. 53: 65-144.
Grinnell, F., Billingham, R. E., and Burgess, L. (1981) Distribution of fibronectin during wound healing in vivo. J. Invest. Dermatol. 76: 181-189.
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. (2000) Fibroblast-collagen matrix contraction: Growth factor signalling and mechanical loading. Trends in Cell Biology. 10: 362-365.
Grinnell, F. (2003) Fibroblast biology in three-dimensional collagen matrices. Trends in Cell Biology. 13: 264-269.