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 3Nuclear fragility is increased in lamin A/C–deficient cells. (
a and
b) Fluorescently labeled 70-kDa dextran is excluded from the nucleus following cytoplasmic injection, indicating an intact nuclear membrane in WT (
a) and
Lmna–/– (
b) cells under resting conditions. Scale bar: 20 μm. (
c) Nuclear injection at low pressure results in fluorescently labeled dextran contained in the nucleus of WT cells, indicating that the nuclear integrity is preserved during injection. Scale bar: 20 μm. (
d) In contrast, nuclear integrity is disrupted in nuclei of
Lmna–/– cells even at low pressure, leading to fluorescently labeled dextran escaping into the cytoplasm during injection. Scale bar: 20 μm. (
e) Nuclear rupture as a function of increasing injection pressure of dextran microinjection into the nucleus. Zero pressure: cytoplasmic injection at 500 hPa. Low pressure: nuclear injection at 10–20 hPa (**84.7% ± 4.24% vs. 9.5% ± 4.53% intact nuclei for WT and
Lmna–/– cells, respectively;
P < 0.0001,
n = 72 [WT], 42 [
Lmna–/–]). Medium pressure: nuclear injection at 100–500 hPa (*40.4% ± 7.16% vs. 9.5% ± 4.53% intact nuclei for WT and
Lmna–/– cells respectively;
P < 0.01,
n = 47 [WT], 31 [
Lmna–/–]). High pressure: nuclear injection at 1,500 hPa; all cells showed nuclear rupture.
