VIFs provide mechanical resistance and protection against compressive forces. (a and b) Schematic for the AFM measurements on vim^+/+, vim^−/−, and rescued mEFs. The average Young’s modulus of the vim^−/− mEFs is lower than those of vim^+/+ mEFs (P < 0.04) and rescued mEFs (b; P < 0.01; vim^+/+ [n = 55], vim^−/− [n = 80], and rescued [n = 20] from n = 2 experiments). The lower and upper parts of the box represent the 25th and 75th percentiles. The ends of the notch indicate 1.57 times the interquartile range divided by the square root of the number of samples. The whiskers indicate the range of the circular variance up to 1.5 times the interquartile range away from the quartiles. (c) Schematic image for external compression of a model system of mEFs cultured in 3D collagen gels; the gels are compressed with a parallel plate rheometer at varying degrees of axial strain. (d) Cells are stained with propidium iodide to determine the amount of necrotic cell death, as shown for 80% compression. Scale bar is 100 µm. (e) Vim^−/− mEFs exhibit more necrosis at large strains compared with the vim^+/+ mEFs, indicating that VIF protect the structural integrity of the cell by resisting large compressive strains (n = 300–700 per condition from n = 2 independent experiments).