Istituto di Biofisica - Consiglio Nazionale delle Ricerche, Via De Marini 16, 16149 Genova, Italy.
EMPA, Swiss Federal Laboratories for Materials Science and Technology, Ueberlandstrasse 129, 8600 Dübendorf, Switzerland; ETH Zurich, The Institute for Mechanical Systems, Leonhardstrasse 21, 8092 Zürich, Switzerland.
Biomater Adv. 2023 May;148:213355. doi: 10.1016/j.bioadv.2023.213355. Epub 2023 Feb 23.
Visceral myopathy (VSCM) is a rare genetic disease, orphan of pharmacological therapy. VSCM diagnosis is not always straightforward due to symptomatology similarities with mitochondrial or neuronal forms of intestinal pseudo-obstruction. The most prevalent form of VSCM is associates with variants in the gene ACTG2, encoding the protein gamma-2 actin. Overall, VSCM is a mechano-biological disorder, in which different genetic variants lead to similar alterations to the contractile phenotype of enteric smooth muscles, resulting in the emergence of life-threatening symptoms. In this work we analyzed the morpho-mechanical phenotype of human dermal fibroblasts from patients affected with VSCM, demonstrating that they retain a clear signature of the disease when compared with different controls. We evaluated several biophysical traits of fibroblasts, and we show that a measure of cellular traction forces can be used as a non-specific biomarker of the disease. We propose that a simple assay based on traction forces could be designed to provide a valuable support for clinical decision or pre-clinical research.
内脏肌病（VSCM）是一种罕见的遗传性疾病，缺乏药物治疗方法。由于与线粒体或神经元形式的假性肠梗阻的症状相似，VSCM 的诊断并不总是很直接。VSCM 最常见的形式与编码蛋白γ-2 肌动蛋白的基因 ACTG2 中的变体有关。总的来说，VSCM 是一种机械生物学障碍，其中不同的遗传变异导致肠平滑肌收缩表型发生相似的改变，从而出现危及生命的症状。在这项工作中，我们分析了患有 VSCM 的患者的人真皮成纤维细胞的形态力学表型，证明与不同对照相比，它们仍然保留了疾病的明显特征。我们评估了成纤维细胞的几种生物物理特性，并表明细胞牵引力的测量可以用作疾病的非特异性生物标志物。我们提出，可以设计一种基于牵引力的简单测定法，为临床决策或临床前研究提供有价值的支持。
