Cellular and Matrix Contributions to Tissue Construct Stiffness Increase with Cellular Concentration

Abstract

The mechanics of bio-artificial tissue constructs result from active and passive contributions of cells and extracellular matrix (ECM). We delineated these for a fibroblast-populated matrix (FPM) consisting of chick embryo fibroblast cells in a type I collagen ECM through mechanical testing, mechanical modeling, and selective biochemical elimination of tissue components. From a series of relaxation tests, we found that contributions to overall tissue mechanics from both cells and ECM increase exponentially with the cell concentration. The force responses in these relaxation tests exhibited a logarithmic decay over the 3600 second test duration. The amplitudes of these responses were nearly linear with the amplitude of the applied stretch. The active component of cellular forces rose dramatically for FPMs containing higher cell concentrations.

Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

“…We believe that this is due to loading cells through their natural structural networks in these three-dimensional tissue constructs, as opposed to probing the membrane as must be done when testing cell mechanics in two-dimensional cultures. Our predictions indicated that cell moduli decreased appreciably with increasing cell concentration to levels as low as 10 kPa for the highest cell concentrations attainable in this system, suggesting that cells remodel in response to changes in their mechanical environment; although earlier work showed that the overall cellular contribution to tissue construct mechanics increases with increasing cellular volume fraction (Marquez et al 2006b), this is due to a diminished contribution from each member of a larger population of cells. These changes could be a combination of active and passive effects.…”

“…Cell populations in these tissue constructs were observed to increase or decrease in size to approach the percolation threshold, at which a contiguous steric network of cells is predicted (Marquez et al 2006b). The observation in this work that the cell and ECM effective moduli converge at the percolation threshold bears further investigation in the context of observations of Discher et al (2005) on cellular adaptation to the ECM modulus.…”

“…Bell et al 1979;Kolodney & Wysolmerski 1992;Asnes et al 2006;Griffith & Swartz 2006). Contractile fibroblast cells within a collagen gel can remodel and compact the collagen ECM around them, resulting in a stiffening of the tissue construct (Isenberg & Tranquillo 2003;Pryse et al 2003;Marquez et al 2006b). Because these tissue constructs capture the strong interaction between cell and ECM components, these systems are preferable to studies of isolated cells.…”

Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds

“…Several studies have reported that cell attachment, proliferation and differentiation are all modulated by the substrate rigidity to a degree dependent upon the substrate stiffness in relation to the stiffness of the native tissunmee (Engler et al, 2006;Khatiwala et al, 2007). In addition, at the tissue-implant interface, cells can actively modify surfaces of the implants, altering the stiffness of microenviront of their own or other cells (Marquez et al, 2006). Tan and Teoh demonstrated that 3T3 fibroblasts preferred soft surface for proliferation.…”

Development of DNA Based Active Macro–Materials for Biology and Medicine: A Review

“…Moreover, aging, development, external assault, and pathological processes can also lead to the alternations in the extracellular matrix (ECM) (Georges et al 2007, Ingber 2002, Silver et al 2003. In addition, at the tissue-implant interface, cells can actively modify surface of the implants, altering the stiffness of microenvironment of their own or other cells (Marquez et al 2006). The changing stiffness could potentially make it possible to achieve optimal growth of a specific cell property (Jiang et al 2008b) or direct stem cell differentiation (Engler et al 2006) at different time points.…”