ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

COMPUTATIONAL MODELING OF TANGLED AND UNTANGLED
COLLAGEN FIBER GELS
X. Ma 1 , K.J. Gooch, 2 S.N. Ghadiali, 2 and R.T. Hart 3
1. ABSTRACT
We are investigating the potential for living cells that are embedded in extracellular
matrix material to communicate mechanically over relatively long distances, e.g., 10 or
more cell diameters. Our experimental work is focused on imaging fibroblast-seeded
collagen gels (consisting of fibers plus the surrounding matrix material) and monitoring
collagen fiber reorganization that occurs between 4 and 24 hours after seeding. We have
generated 2D images to build finite element models to examine the force and stress
transmission in the fibers (Ma, et. al, 2011a,b). We have also examined the stresses and
forces in idealized 2D finite element models of collagen fiber networks, and varied the
fiber number, length, thickness, and orientation of fibers to see their influence (Ma, et.
al, 2009a). The key parameter whose influence we have not been able to address with
2D models is the effect of cross-linking in the fiber network; in many of our previous
models, all of the fibers that cross or touch are assumed to be tangled and essentially
“welded” together where they touch. We have previously taken steps to address this
limitation by using stacked “layers” of a thin fluid matrix, with embedded fibers that do
not connect or intersect, as part of a 3D model (Ma, et. al, 2009b). However, the
boundary conditions, with fluid flow in the plane of the layers, may not be a good
analogue for studying the mechanics of the cell-cell communication phenomena. The
idealized solid mechanics models presented here demonstrate that stress transmission
between cells is dominated by the presence of tangled fibers and that similar networks
with untangled fibers are much less effective in transmitting stresses.
2. INTRODUCTION
Previous experimental studies have suggested that extra cellular matrix (ECM) fibers
can effectively transmit mechanical forces over long distances. It has been proposed that
during vascular morphogenesis, the elastic interactions between fibrils allow the
transmission of stress over a significant range (Vernon, et. al, 1995) so that the ECM
serves as a 3D scaffold for individual endothelial cells (ECs) and clusters of ECs
transducing mechanical forces to other ECs at a considerable distance. Thus, ECs may
establish tension-based guidance pathways that provide a mechanism for them to
organize into large multicellular structures and communicate over a long distances
without the initial requirement of cell-cell contact (Davis, et. al, 1996 and Davis, et. al,
2005). Consistent with this view, capillary sprouts in vivo preferentially follow ECM
fibers (Anderson, et. al, 2004). Additionally, isolated corneal fibroblasts align and
compact collagen fibers parallel to the axis of greatest effective stiffness. This effect
1
Doctoral Student, Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio,
43210, USA
2
Associate Professor, Department of Biomedical Engineering, The Ohio State University, Columbus,
Ohio, 43210, USA
3
Professor and Chair, Department of Biomedical Engineering, The Ohio State University, Columbus,
Ohio, 43210, USA