BACKGROUND:Laminopathies are genetic diseases caused by mutations in the nuclear lamina. OBJECTIVE:Given the clinical impact of laminopathies, understanding mechanical properties of cells bearing lamin mutations will lead to advancement in the treatment of heart failure. METHODS:Atomic force microscopy (AFM) was used to analyze the viscoelastic behavior of neonatal rat ventricular myocyte cells expressing three human lamin A/C gene (LMNA) mutations. RESULTS:Cell storage modulus was characterized, by two plateaus, one in the low frequency range, a second one at higher frequencies. The loss modulus instead showed a “bell” shape with a relaxation toward fluid properties at lower frequencies. Mutations shifted the relaxation to higher frequencies, rendering the networks more solid-like. This increase of stiffness with mutations (solid like behavior) was at frequencies around 1 Hz, close to the human heart rate. CONCLUSIONS:These features resulted from a combination of the properties of cytoskeleton filaments and their temporary cross-linker. Our results substantiate that cross-linked filaments contribute, for the most part, to the mechanical strength of the cytoskeleton of the cell studied and the relaxation time is determined by the dissociation dynamics of the cross-linking proteins. The severity of biomechanical defects due to these LMNA mutations correlated with the severity of the clinical phenotype.

中文翻译：

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携带LMNA突变的心肌细胞的粘弹性行为。

背景：椎间盘突出症是由核层板突变引起的遗传性疾病。目的：鉴于椎间盘突出症的临床影响，了解带有lamin突变的细胞的机械特性将导致心力衰竭的治疗进展。方法：采用原子力显微镜（AFM）分析表达三种人lamin A / C基因（LMNA）突变的新生大鼠心室肌细胞的粘弹性行为。结果：细胞储能模量的特征在于两个平稳段，一个处于低频范围，第二个处于较高频率。损耗模量显示为“钟形”形状，在较低频率下对流体特性有松弛。突变将弛豫转移到更高的频率，使网络更像实体。刚度随突变而增加（类似固体的行为）的频率约为1 Hz，接近人类的心律。结论：这些特征是由细胞骨架丝及其临时交联剂的特性共同导致的。我们的结果证实，交联的细丝在很大程度上有助于所研究细胞的细胞骨架的机械强度，弛豫时间取决于交联蛋白的解离动力学。由于这些LMNA突变而引起的生物力学缺陷的严重程度与临床表型的严重程度相关。我们的结果证实，交联的细丝在很大程度上有助于所研究细胞的细胞骨架的机械强度，弛豫时间取决于交联蛋白的解离动力学。由于这些LMNA突变而引起的生物力学缺陷的严重程度与临床表型的严重程度相关。我们的结果证实，交联的细丝在很大程度上有助于所研究细胞的细胞骨架的机械强度，弛豫时间取决于交联蛋白的解离动力学。由于这些LMNA突变而引起的生物力学缺陷的严重程度与临床表型的严重程度相关。