Many biological consequences of external mechanical loads applied to cells depend on localized cell deformations rather than on average whole-cell-body deformations. Such localized intracellular deformations are likely to depend, in turn, on the individual geometrical features of each cell, e.g., the local surface curvatures or the size of the nucleus, which always vary from one cell to another, even within the same culture. Our goal here was to characterize cell-to-cell variabilities in magnitudes and distribution patterns of localized tensile strains that develop in the plasma membrane (PM) and nuclear surface area (NSA) of compressed myoblasts, in order to identify resemblance or differences in mechanical performances across the cells. For this purpose, we utilized our previously developed confocal microscopy-based three-dimensional cell-specific finite element modeling methodology. Five different C2C12 undifferentiated cells belonging to the same culture were scanned confocally and modeled, and were then subjected to compression in the simulation setting. We calculated the average and peak tensile strains in the PM and NSA, the percentage of PM area subjected to tensile strains above certain thresholds and the coefficient of variation (COV) in average and peak strains. We found considerable COV values in tensile strains developing at the PM and NSA (up to ∼35%) but small external compressive deformations induced greater variabilities in intracellular strains across cells compared to large deformations. Interestingly, the external deformations needed to cause localized PM or NSA strains exceeding each threshold were very close across the different cells. Better understanding of variabilities in mechanical performances of cells—either of the same type or of different types—is important for interpreting experimental data in any experiments involving delivery of mechanical loads to cells.

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