Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction
J. Clin. Invest. Jan Lammerding, et al. 113:370 doi:10.1172/JCI19670 [
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Figure 2Cytoskeletal stiffness is reduced in lamin A/C–deficient cells. (
a) Phalloidin staining for actin stress fibers in WT (
Lmna+/+) fibroblasts. Scale bar: 20 μm. (
b) Phalloidin staining for actin stress fibers in
Lmna–/– cells. Scale bar: 20 μm. (
c) Magnetic bead microrheology. Representative examples of magnetic bead displacement in response to applied sinusoidal force (thin black line) for WT (thick black line) and
Lmna–/– (thick gray line) fibroblasts. (
d) Bead displacement amplitude in response to applied magnetic forces was significantly increased in
Lmna–/– fibroblasts, indicating reduced cytoskeletal stiffness in lamin A/C–deficient cells (0.124 ± 0.024 μm vs. 0.226 ± 0.029 μm;
P < 0.01,
n = 60). (
e) Fibroblast with magnetic (diameter 4.5 μm) and polystyrene beads (diameter 2 μm) attached to the cell membrane. Scale bar: 10 μm. (
f) Graphic representation of the displacement field after a brief force pulse (2.5 nN for 3 seconds). Bead sizes and positions are drawn to scale, while bead deflections are enlarged by a factor of 10. (
g and
h) Distance dependence of the angle-corrected radial bead displacement component
ur/cosθ as defined in equation 1. The dotted line is an optimal fit to equation 1, yielding estimates for cellular stiffness
μ* and dissipation κ for WT (
g) and
Lmna–/– cells (
h), respectively (
μ*: 27,537 ± 8,458 pN/μm vs. 2,417 ± 734.7 pN/μm;
P < 0.01,
n = 128 [WT], 153 [
Lmna–/–]; κ: 0.020 ± 0.017 μm
–1 vs. 0.201 ± 0.072 μm
–1;
P < 0.05,
n = 128 [WT], 153 [
Lmna–/–]). pN, piconewton.