Noncooperative cell behaviorA brief review or relevant structures: cell membrane, transmembrane proteins, cell receptors (integrins), cytoplasm, matrixConclusions on Linearity vs. Cooperativity of Fibroblast Contraction of Matrix Conclusions on Micromechanics of Fibroblast ContractionConclusions on the Effect of Matrix Stiffness on Cell ContractionNoncooperative cell behaviorUnder certain conditions cells interact with the biomaterial surface each individuallyA brief review or relevant structures: cell membrane, transmembrane proteins, cell receptors (integrins), cytoplasm, matrixDefinition of unit cell processCell +InsolubleRegulatorProductSolubleRegulator BSolubleRegulator AFigure by MIT OpenCourseWare.Control volume dVUnit cell process confined conceptually in a control volume dVA typified cell diagramshowing cell-cell bindingDiagram removed due to copyright restrictions.Cell membranesketchshowing transmem-brane proteinsFigure by MIT OpenCourseWare.Figure by MIT OpenCourseWare.Figure by MIT OpenCourseWare.Another model of a specific cell-matrix interactionDiagram of fibronectin attaching cell to surface of collagen fiber removed due to copyright restrictions.View of cytoplasmPhoto image removed due to copyright restrictions.100 μm 100 μm A biologically active ECM analogCells pull matrixPhoto image removed due to copyright restrictions.FIRST ARTICLEModified cell force monitor used to study cell-matrix interactions quantitativelyAluminum Base PlateSiliconeCulture MediumStrainGaugesAdjustableHeightPostCollagenMatrixFigure by MIT OpenCourseWare.Use to study unit cell processes quantitativelyFreyman et al., 2001Source: Freyman, T. M., I. V. Yannas, R. Yokoo, and L. J. Gibson. "Fibroblast contraction of a collagen-GAG matrix."Biomaterials 22 (2001): 2883-2891. Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Source: Freyman, T. M., I. V. Yannas, R. Yokoo, and L. J. Gibson."Fibroblast contraction of a collagen-GAG matrix." Biomaterials 22 (2001): 2883-2891.Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Source: Freyman, T. M., I. V. Yannas, R. Yokoo, and L. J. Gibson. "Fibroblast contraction of a collagen-GAG matrix."Biomaterials 22 (2001): 2883-2891. Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Conclusions on Linearity vs. Cooperativity of Fibroblast Contraction of Matrix• The contractile force increases linearly with cell density.• The average contractile force is calculated at 1 nN per cell.• The time constant for development of force is also independent of cell density. • In this model cells must develop contractile forces individually, not cooperatively.SECOND ARTICLESlides with images removed due to copyright restrictions.See Fig 2 (schematic of imaging setup), Fig. 4 and Fig. 5 (graphs of results).In Freyman et al. “Micromechanics of Fibroblast Contraction of a Collagen–GAG Matrix.” Exp Cell Res 269, no. 1 (2001): 140-153.http://dx.doi.org/10.1006/excr.2001.5302Sequence showing a cell (arrow A)simultaneouslyelongating and deforming a matrix strut (arrow B)Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Another sequence showing a cell (A) elongating and deforming matrix struts (B)Photos removed due to copyright restrictions.See Fig. 7 in Freyman et al. “Micromechanics of Fibroblast Contraction of a Collagen–GAG Matrix.” Exp Cell Res 269, no. 1 (2001): 140-153.http://dx.doi.org/10.1006/excr.2001.5302Sequence showscell (A) elongating on matrix strut (B). Later, adhesion sites near cell center are released (C); eventually one end of cell fails to attach and the cell retracts rapidly (D). Later, the cell elongates once more (E) and the process is repeated.Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Live Cell Imaging2 min50 μm19 min23 min25 min26 min28 min33 min38 min3 hours42 minFreyman et al., 2001Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.struts for a given displacement imposed by the cell. Note that following the onsetof buckling, resistive force does not increase significantlyfor increase in deformation.Courtesy of Elsevier, Inc.,http://www.sciencedirect.com.Used with permission.Conclusions on Micromechanics of Fibroblast Contraction• The aspect ratio of cells increases with time and eventually saturates, just as the force does. • Initiation of cell elongation occurs stochastically. • The force plateau most simply results from buckling or bending of individual struts in the matrix by cells. • Matrix deformation (contraction) occurs as a result of cell elongation, not cell contraction.THIRD ARTICLEImages removed due to copyright restrictions.Tables 1 and 2, Figures 2, 3 and 4 in Freyman, T. M., et al. "Fibroblast Contractile Force Is Independent of the Stiffness Which Resists the Contraction." Exp Cell Res 272 (2002): 153-162.http://dx.doi.org/10.1006/excr.2001.5408Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.Conclusions on the Effect of Matrix Stiffness on Cell Contraction• The contractile force generated by fibroblasts was independent of matrix stiffness in the range 0.7 – 10.7 N/m.• Contractile forces generated by cells are force-limited, not displacement-limited. • As cells elongate, cell-matrix adhesion sites hypothetically form at the cell periphery, increasing length of matrix strut under compressive load and decreasing load required to buckle the strut.MIT OpenCourseWarehttp://ocw.mit.edu 20.441J / 2.79J / 3.96J / HST.522J Biomaterials-Tissue InteractionsFall 2009For information about citing these materials or our Terms of Use, visit: