Multiscale Modeling and Biomechanical Analysis of Animal Cells

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This research will reveal quantitative connections between geometry and material properties of cell constituents. This work will also study the responses of cells to mechanical loads. Sensitivity to mechanical forces is a general feature of all living cells, tissues, and organs. Unhealthy cells exhibit different mechanical properties than healthy ones. For example, most cancer cells are more deformable than their noncancerous counterparts. However, the mechanisms underlying the reaction of biological systems to applied loads are not well characterized. The dominant factors controlling cell mechanical properties remain unknown. This work will produce a quantitative model that describes cell reactions to the applied forces. The approach will combine numerical, theoretical and experimental methods. The resulting model may be used for the future development of rapid diagnostic methods for various diseases such as cancer and Alzheimer’s disease. Results from this research will immediately benefit society with fundamental knowledge on the rules of life. In the long term, the knowledge and working model can be used to further the health of the nation. The project will build research capacity at New Mexico State University, a land grant Hispanic serving research institution. The research will be performed by an interdisciplinary team of investigators and trainees with expertise in computational chemistry, micromechanics, and cellular biology. To date, cellular biomechanics research has been focused on acquisition of experimental data characterizing cellular properties, with lesser emphasis on developing theoretical frameworks that can explain the observable responses of cells to mechanical forces. The present project bridges this knowledge gap by implementing multiscale modeling to analysis of cellular biomechanics. The ultimate goal is to produce a multiscale model of an animal cell that can be used to formulate predictions, develop testable hypotheses, and uncover insights into the mechanisms by which cells react to the external forces. This goal will be achieved through completion of the following objectives: (1) determination of the mechanical properties of cell components, (2) development of a micromechanical model of the viscoelastic properties of cells, and (3) experimental validation of the developed model. To meet objectives (1) and (2), a combination of methods of molecular dynamics and micromechanics will be used. To meet objective (3), atomic force microscopy of a wide variety of animal cells from different species will be used. This project is jointly funded by the Biomechanics & Mechanobiology (BMMB) Program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.