Energy landscape view of fracture and avalanches in disordered materials.

Molecular simulations are carried out to probe how strain-induced changes in the energy landscape are related to fracture processes in disordered systems. The simulations address a two-dimensional system that consists of 9952 particles with a distribution of sizes, and the changes in the structure and properties with strain are determined with the system constrained to an energy minimum. As the system is strained, local minima of the energy landscape are found to flatten out and disappear, which causes discontinuous structural rearrangements. These structural rearrangements, which correspond to avalanche events, lead to void nucleation and crack growth in discrete steps.

Energy landscapes and the non-Newtonian viscosity of liquids and glasses.

An inherent structure analysis of viscosity is developed based on results of nonequilibrium molecular dynamics simulations. The viscosity is separated into a "structural" contribution associated with the energy minima that the system visits, and a "vibrational" contribution associated with displacements within the energy minima. The structural contribution is shear thinning due to strain-activated relaxations caused by the disappearance of high-stress energy minima, while the vibrational contribution is Newtonian.

Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human prostate cancer cells.

The in vitro self-assembly of multicellular spheroids generates highly organized structures in which the three-dimensional structure and differentiated function frequently mimic that of in vivo tissues. This has led to their use in such diverse applications as tissue regeneration and drug therapy. Using Smoluchowski-like rate equations, herein we present a model of the self-aggregation of DU 145 human prostate carcinoma cells in liquid-overlay culture to elucidate some of the physical parameters affecting homotypic aggregation in attachment-dependent cells. Experimental results indicate that self-aggregation in our system is divided into three distinct phases: a transient reorganization of initial cell clusters, an active aggregation characterized by constant rate coefficients, and a ripening phase of established spheroid growth. In contrast to the diffusion-controlled aggregation previously observed for attachment-independent cells, the model suggests that active aggregation in our system is reaction-controlled. The rate equations accurately predict the aggregation kinetics of spheroids containing up to 30 cells and are dominated by spheroid adhesive potential with lesser contributions from the radius of influence. The adhesion probability increases with spheroid size so that spheroid-spheroid adhesions are a minimum of 2.5 times more likely than those of cell-cell, possibly due to the upregulation of extracellular matrix proteins and cell-adhesion molecules. The radius of influence is at least 1.5 to 3 times greater than expected for spherical geometry as a result of ellipsoidal shape and possible chemotactic or Fröhlich interactions. Brownian-type behavior was noted for spheroids larger than 30 microm in diameter, but smaller aggregates were more motile by as much as a factor of 10 for single cells. The model may improve spheroid fidelity for existing applications of spheroids and form the basis of a simple assay for quantitatively evaluating cellular metastatic potential as well as therapies that seek to alter this potential.

Regressive biological evolution due to environmental change.

Simulation results are presented which suggest that regressive evolution (i.e., evolution to a less adapted state) often occurs in response to environmental change, by a process analogous to the stress-induced reversal of aging in glassy materials. The key to this process is the stress-induced disappearance of fitness optima that lead to irreversible changes in the location of a population in genotype space. Even though the population may always evolve to higher fitness states, this irreversible process will often act to bring an initially well-adapted system to a less adapted state upon a return to initial conditions.

Characterization of aggregation and protein expression of bovine corneal endothelial cells as microcarrier cultures in a rotating-wall vessel.

Rotating-wall vessels are beneficial to tissue engineering in that the reconstituted tissue formed in these low-shear bioreactors undergoes extensive three-dimensional growth and differentiation. In the present study, bovine corneal endothelial (BCE) cells were grown in a high-aspect rotating-wall vessel (HARV) attached to collagen-coated Cytodex-3 beads as a representative monolayer culture to investigate factors during HARV cultivation which affect three-dimensional growth and protein expression. A collagen type I substratum in T-flask control cultures increased cell density of BCE cells at confluence by 40% and altered the expression of select proteins (43, 50 and 210 kDa). The low-shear environment in the HARV facilitated cell bridging between microcarrier beads to form aggregates containing upwards of 23 beads each, but it did not promote multilayer growth. A kinetic model of microcarrier aggregation was developed which indicates that the rate of aggregation between a single bead and an aggregate was nearly 10 times faster than between two aggregate and 60 times faster than between two single beads. These differences reflect changes in collision frequency and cell bridge formation. HARV cultivation altered the expression of cellular proteins (43 and 70 kDa) and matrix proteins (50, 73, 89 and 210 kDa) relative to controls perhaps due to hypoxia, fluid flow or distortion of cell shape. In addition to the insight that this work has provided into rotating-wall vessels, it could be useful in modeling aggregation in other cell systems, propagating human corneal endothelial cells for eye surgery and examining the response of endothelial cells to reduced shear.