Development of a Computational Model for Cell Activity in a Nano-Scaffold

Tissue engineering utilizes nano-scaffolds to direct cell growth and control cell behavior. Since cells occupy specific spaces within extracellular matrix (ECM) it’s important to understand how the geometry of these spaces influence cell behaviors such as movement, death and proliferation. Understanding how the 3-dimensional geometry created by the alignment and density of fibers within the scaffold dictates cell behavior can ultimately lead to scaffold design which promotes more rapid and complete healing. However due to the constraints surrounding bioactive implants and their experimental status there exists little data on how effective nano-scaffolds have performed. The goal of this research is to outline how a computational model can accurately simulate cell behavior within a nano-scaffold to better optimize scaffold parameters. Therefore, this research will examine fiber deposition, degradation, and realignment by cells in a scaffold. Additionally, this research will also cover programmed cell behavior such as movement, death and proliferation. Incorporating this knowledge into scaffold design could aid in the advancement of regenerative medicine and shape the future of tissue engineering

Dielectric Behavior of Nonspherical Cell Suspensions

Recent experiments revealed that the dielectric dispersion spectrum of fission yeast cells in a suspension was mainly composed of two sub-dispersions. The low-frequency sub-dispersion depended on the cell length, whereas the high-frequency one was independent of it. The cell shape effect was qualitatively simulated by an ellipsoidal cell model. However, the comparison between theory and experiment was far from being satisfactory. In an attempt to close up the gap between theory and experiment, we considered the more realistic cells of spherocylinders, i.e., circular cylinders with two hemispherical caps at both ends. We have formulated a Green function formalism for calculating the spectral representation of cells of finite length. The Green function can be reduced because of the azimuthal symmetry of the cell. This simplification enables us to calculate the dispersion spectrum and hence access the effect of cell structure on the dielectric behavior of cell suspensions.Comment: Preliminary results have been reported in the 2001 March Meeting of the American Physical Society. Accepted for publications in J. Phys.: Condens. Matte

Wettability influences cell behavior on superhydrophobic surfaces with different topographies

Surface wettability and topography are recognized as critical factors influencing cell behavior on biomaterials. So far only few works have reported cell responses on surfaces exhibiting extreme wettability in combination with surface topography. The goal of this work is to study whether cell behavior on superhydrophobic surfaces is influenced by surface topography and polymer type. Biomimetic superhydrophobic rough surfaces of polystyrene and poly(l-lactic acid) with different micro/nanotopographies were obtained from smooth surfaces using a simple phase-separation based method. Total protein was quantified and showed a less adsorption of bovine serum albumin onto rough surfaces as compared to smooth surfaces of the same material. The mouse osteoblastic MC3T3-E1 cell line and primary bovine articular chondrocytes were used to study cell attachment and proliferation. Cells attached and proliferate better in the smooth surfaces. The superhydrophobic surfaces allowed cells to adhere but inhibited their proliferation. This study indicates that surface wettability, rather than polymer type or the topography of the superhydrophobic surfaces, is a critical factor in determining cell behavior

MODELLING THE INFLUENCE OF NUCLEUS ELASTICITY ON CELL INVASION IN FIBER NETWORKS AND MICROCHANNELS

Cell migration in highly constrained extracellular matrices is exploited in scaffold-based tissue engineering and is fundamental in a wide variety of physiological and pathological phenomena, among others in cancer invasion and development. Research into the critical processes involved in cell migration has mainly focused on cell adhesion and proteolytic degradation of the external environment. However, rising evidence has recently shown that a number of cell-derived biophysical and mechanical parameters, among others nucleus stiffness and cell deformability, plays a major role in cell motility, especially in the ameboid-like migration mode in 3D confined tissue structures. We here present an extended cellular Potts model (CPM) first used to simulate a micro-fabricated migration chip, which tests the active invasive behavior of cancer cells into narrow channels. As distinct features of our approach, cells are modeled as compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the migration chamber is composed of channels of different widths. We find that cell motile phenotype and velocity in open spaces (i.e., 2D flat surfaces or large channels) are not significantly influenced by cell elastic properties. On the contrary, the migratory behavior of cells within subcellular and subnuclear structures strongly relies on the deformability of the cytosol and of the nuclear cluster, respectively. Further, we characterize two migration dynamics: a stepwise way, characterized by fluctuations in cell length, within channels smaller than nucleus dimensions and a smooth sliding (i.e., maintaining constant cell length) behavior within channels larger than the nuclear cluster. These resulting observations are then extended looking at cell migration in an artificial fiber network, which mimics cell invasion in a 3D extracellular matrix. In particular, in this case, we analyze the effect of variations in elasticity of the nucleus on cell movement. In order to summarize, with our simulated migration assays, we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the cytoskeletal and nuclear elastic characteristics correlate with the tumor cell's invasive potentia

Turbulent Cells in Stars: I. Fluctuations in Kinetic Energy and Luminosity

Three-dimensional (3D) hydrodynamic simulations of shell oxygen burning (Meakin and Arnett, 2007b) exhibit bursty, recurrent fluctuations in turbulent kinetic energy. These are shown to be due to a general instability of the convective cell, requiring only a localized source of heating or cooling. Such fluctuations are shown to be suppressed in simulations of stellar evolution which use mixing-length theory (MLT). Quantitatively similar behavior occurs in the model of a convective roll (cell) of Lorenz (1963), which is known to have a strange attractor that gives rise to chaotic fluctuations in time of velocity and, as we show, luminosity. Study of simulations suggests that the behavior of a Lorenz convective roll may resemble that of a cell in convective flow. We examine some implications of this simplest approximation, and suggest paths for improvement. Using the Lorenz model as representative of a convective cell, a multiple-cell model of a convective layer gives total luminosity fluctuations which are suggestive of irregular variables (red giants and supergiants (Schwarzschild 1975)), and of the long secondary period feature in semi-regular AGB variables (Stothers 2010, Wood, Olivier and Kawaler 2004). This "tau-mechanism" is a new source for stellar variability, which is inherently non-linear (unseen in linear stability analysis), and one closely related to intermittency in turbulence. It was already implicit in the 3D global simulations of Woodward, Porter and Jacobs (2003). This fluctuating behavior is seen in extended 2D simulations of CNeOSi burning shells (Arnett and Meakin 2011b), and may cause instability which leads to eruptions in progenitors of core collapse supernovae PRIOR to collapse.Comment: 30 pages, 13 figure

Correlating Cell Behavior with Tissue Topology in Embryonic Epithelia

Measurements on embryonic epithelial tissues in a diverse range of organisms have shown that the statistics of cell neighbor numbers are universal in tissues where cell proliferation is the primary cell activity. Highly simplified non-spatial models of proliferation are claimed to accurately reproduce these statistics. Using a systematic critical analysis, we show that non-spatial models are not capable of robustly describing the universal statistics observed in proliferating epithelia, indicating strong spatial correlations between cells. Furthermore we show that spatial simulations using the Subcellular Element Model are able to robustly reproduce the universal histogram. In addition these simulations are able to unify ostensibly divergent experimental data in the literature. We also analyze cell neighbor statistics in early stages of chick embryo development in which cell behaviors other than proliferation are important. We find from experimental observation that cell neighbor statistics in the primitive streak region, where cell motility and ingression are also important, show a much broader distribution. A non-spatial Markov process model provides excellent agreement with this broader histogram indicating that cells in the primitive streak may have significantly weaker spatial correlations. These findings show that cell neighbor statistics provide a potentially useful signature of collective cell behavior.Comment: PLoS one 201