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

COMPUTATIONAL STUDY OF THE EFFECTS OF CELL SHAPE AND
SIZE ON MIGRATION IN A THREE-DIMENSIONAL MATRIX
1. ABSTRACT
H. C. Wong 1 and W. C. Tang 2
Cancer metastasis, wound healing, and the immune response are facilitated with cell
migration. Though many computer models have been used to study the effects of
extracellular matrix (ECM) degradation on 3D cell migration, more studies are needed
to investigate the impact of cell shape and size on these models. In our work, the cell
was modeled as an ellipsoid where the aspect ratio was defined as the semi-axis in the
direction of migration divided by that in the transverse directions. The cases where the
cell–ECM adhesion coefficient was constant or dependent on cellular dimensions were
considered. Results showed that cells migrated faster and at higher ECM densities as
they elongated in the direction of migration. When the adhesion coefficient and cell–
ECM tractions increased with the semi-axis of the cell in the direction of migration, cell
speed peaked at a higher degradation coefficient for the case where the aspect ratio was
greater than one. It would be of interest to investigate how cell shape and size impact
actin-based and amoeboid cell migration behaviors in a 3D environment. With these
additional considerations, this modeling effort would represent a crucial step in
improving our understanding of how cells move in their native environment.
2. INTRODUCTION
Cancer metastasis, wound healing, and the immune response are facilitated with cell
migration [1]. It is a coordinated process that involves adhesion to the extracellular
matrix (ECM) in order to exert forces that are needed for the cell to move in a specific
direction. These forces arise from the contraction of the cell’s intracellular actomyosin
cytoskeleton [2]. The sites of cell–ECM contact are known as focal adhesions, which are
complexes that consist of many different proteins. These include the integrin receptors
that can selectively bind to ECM ligands, such as fibronectin [3]. Cells that utilize the
mesenchymal mode of migration in a 3D space secrete matrix metalloproteinases
(MMPs) that partially degrade the components in the ECM in order to construct a path
for them to migrate through [4]. Cell shape and size have also been shown to be an
important indicator of cell function, and are determined by the cell’s cytoskeleton and its
adhesions to the ECM [5].
Though many computer models have been published that studied the effects of ECM
degradation on cell migration [6, 7, 8], more studies are needed to investigate the impact
of cell shape and size on these models. In particular, there is a need to study how the
1
Ph.D. Candidate, Department of Biomedical Engineering, University of California, Irvine, 3120 Natural
Sciences II, Irvine, California, USA 92697-2715
2
Professor, Department of Biomedical Engineering and Electrical Engineering and Computer Science,
University of California, Irvine, 3120 Natural Sciences II, Irvine, California, USA 92697-2715