POWRE: Mechanics of Biological Cell and Cell-Cell Interactions: Microstructural Models

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9973608MoonIn vivo monitoring of biological cell elasticity offers potentially powerful techniques for non-invasive, early cancer detection. It is currently believed that cells which undergo a malignant transformation (normal to cancerous) simultaneously undergo subtle changes in their cytoskeleton, resulting in loss of mobility and stiffness. The internal structure and organization of eukaryotic (human) cells is largely governed by a structure known as the actin cytoskeleton (AC). The AC can be roughly divided into two superimposing elastic elements: a homogeneous filamentous protein network, the actin cortex, which underlies the plasma membrane, and stress fibers which span the entire cell interior. The AC is suspected of being chiefly responsible for a cell's elastic strength, so its disruption is thought to destabilize a cell's shape and diminish its mobility. Eukaryotic cytoskeletal models and experiments will be developed to determine whether the cell's AC is chiefly responsible for its strength. The AC will be represented by a series of analytical and numerical models with increasingly-detailed, internal "architectural" features mimicking the actin cortex and stress fibers. Key factors to be considered are: AC architecture and AC-constituent behavior. Model predictions will be compared with cell elasticity estimates from an optical stretcher, which uses radiation pressure of two counter-propagating laser beams to trap and non-destructively stretch individual biological cells. At the conclusion of this project, the following will be better understood: 1) the molecular origins of the actin cortex strength; 2) the effect of molecular motors and actin filament stiffness on the mechanical strength of actin networks; and 3) the contribution of the actin network to the overall mechanical strength of eukaryotic cells. This POWRE award will allow the PI to: 1) conduct exploratory work and publish in the area of cell and tissue modeling; 2) learn the relevant language and literature of cell mechanics and molecular biology; 3) pursue a mutually beneficial research collaboration with a biophysicist on the molecular origins of cell elasticity and mobility; 4) become a full-fledged, active participant in the successful Cellular and Biomedical Engineering (CBME) program at The University of Texas at Austin. The POWRE Award comes at an opportune time for the PI, due to the many new opportunities available within UT Austin's Cellular, Molecular Biology and Biomedical Engineering Programs. In 1994, bioengineering was identified as a strategic thrust area. In order to enable the PI's full participation in existing and to-be-developed CBME research projects, she will obtain the necessary, "remedial" cell and molecular biology background; these activities are most appropriate for a POWRE proposal because they would be considered inappropriate for a regular NSF proposal.