Muddana, Hari Shankar (2006-12). Integrated biomechanical model of cells embedded in extracellular matrix. Master's Thesis.
Nature encourages diversity in life forms (morphologies). The study of morphogenesis
deals with understanding those processes that arise during the embryonic development
of an organism. These processes control the organized spatial distribution of cells,
which in turn gives rise to the characteristic form for the organism. Morphogenesis
is a multi-scale modeling problem that can be studied at the molecular, cellular, and
Here, we study the problem of morphogenesis at the cellular level by introducing
an integrated biomechanical model of cells embedded in the extracellular matrix.
The fundamental aspects of mechanobiology essential for studying morphogenesis at
the cellular level are the cytoskeleton, extracellular matrix (ECM), and cell adhesion.
Cells are modeled using tensegrity architecture. Our simulations demonstrate cellular
events, such as differentiation, migration, and division using an extended tensegrity
architecture that supports dynamic polymerization of the micro-filaments of the cell.
Thus, our simulations add further support to the cellular tensegrity model. Viscoelastic
behavior of extracellular matrix is modeled by extending one-dimensional
mechanical models (by Maxwell and by Voigt) to three dimensions using finite element
methods. The cell adhesion is modeled as a general Velcro-type model. We
integrated the mechanics and dynamics of cell, ECM, and cell adhesion with a geometric
model to create an integrated biomechanical model. In addition, the thesis discusses various computational issues, including generating the finite element mesh,
mesh refinement, re-meshing, and solution mapping.
As is known from a molecular level perspective, the genetic regulatory network of
the organism controls this spatial distribution of cells along with some environmental
factors modulating the process. The integrated biomechanical model presented here,
besides generating interesting morphologies, can serve as a mesoscopic-scale platform
upon which future work can correlate with the underlying genetic network.