Finite element analysis reveals an important role for cell morphology in response to mechanical compression.

Mechanical loading naturally controls cell phenotype, development, motility and various other biological functions; however, prolonged or substantial loading can cause cell damage and eventual death. Loading-induced mechanobiological and mechanostructural responses of different cell types affect their morphology and the internal architecture and the mechanics of the cellular components. Using single, mesenchymal stem cells, we have developed a cell-specific three-dimensional finite-element model; cell models were developed from phase-contrast microscopy images. This allowed us to evaluate the mechanostructural response of the naturally occurring variety of cell morphologies to increase sustained compressive loading. We focus on the morphology of the cytoplasm and the nucleus, as the main mechanically responsive elements, and evaluate formation of tensional strains and area changes in cells undergoing increasing uniaxial compressions. Here, we study mesenchymal stem cells as a model, due to their important role in tissue engineering and regenerative medicine; the method and findings are, however, applicable to any cell type. We observe variability in the cell responses to compression, which correlate directly with the morphology of the cells. Specifically, in cells with or without elongated protrusions (i.e., lamellipodia) tensional strains were, respectively, distributed mostly in the thin extensions or concentrated around the stiff nucleus. Thus, through cell-specific computational modeling of mechanical loading we have identified an underlying cause for stiffening (by actin recruitment) along the length of lamellipodia as well as a role for cell morphology in inducing cell-to-cell variability in mechanostructural response to loading.