Long-term dynamic simulation of adipogenic differentiation of a human mesenchymal stem cell.

Multibody dynamic simulations of the mechanobiology of cellular processes have not been obtained for time histories of orders larger than one second even with the employment of supercomputers. A mechanobiologically representative model of a cellular process includes subcellular structures with small masses and lengths. A key development in this work is the inclusion of a coarse-grained representation of the cytoskeleton, based on the tensegrity model, with masses from femtogram to picogram in size and lengths from nanometers to microns in size. A second key development is the inclusion in the model of bodies that increase in mass over time. The forces acting on these bodies will be orders of magnitude larger than the masses. The correspondingly large accelerations necessitate the use of small time steps to obtain an accurate solution. Adipogenic differentiation, adipogenesis, of a human bone marrow-derived mesenchymal stem cell (hMSC) develops over a time span of two weeks in the experiment. Numerically integrating this multiscale model for such a long time period is computationally infeasible with conventional methods. A novel scaling approach based on the method of multiple scales is used herein to accurately simulate this two weeks of time history on a desktop computer in less than 3.5 hours. This much faster than real time simulation facilitates the study of the time dependent elements of adipogenesis and the mechanobiology of cellular processes in general.