Ben-Or Frank Mor, Shoham Naama, Benayahu Dafna, Gefen Amit
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
Biomech Model Mechanobiol. 2015 Jan;14(1):15-28. doi: 10.1007/s10237-014-0582-8. Epub 2014 Apr 5.
Adipogenesis, a process of cell proliferation followed by the accumulation of lipid droplets (LDs), is accompanied by morphological changes in adipocytes, leading to a gradual rise in the structural stiffness of these cells. The increase in cellular structural stiffness can potentially influence the localized deformations of adjacent adipocytes in weight-bearing fat tissues, which, based on previous work, may accelerate intracytoplasmatic lipid production to form even larger and more tightly packed intracellular LDs. This process is based on mechanotransduction phenomena which are hypothesized (again, following empirical studies), to play a critical role in "en mass" adipocyte hypertrophy, and hence are important to characterize through computational modeling. Accordingly, we examined here how maturing adipocytes may affect localized loads acting on adjacent immature cells, using a set of finite element models of adipocytes embedded in an extracellular matrix. The peak strain energy density at the plasma membrane (PM) of the adipocytes, when constructs were externally loaded, was found to depend on the levels of lipid accumulation in the neighboring cells if the external compressive and shear deformations were large enough ([Formula: see text] and [Formula: see text], respectively). The mechanosignaling transduces through the PM and could therefore affect intracellular pathways to produce more lipid contents. Our results support the theory of deformation-induced differentiation in adipocytes. The findings are thus relevant in the context of a sedentary lifestyle, in which sustained deformations of weight-bearing adipose tissues may activate a positive feedback loop that promotes the "en mass" differentiation of cells, which subsequently increases the total mass of living fat tissues.
脂肪生成是一个细胞增殖过程,随后是脂滴(LDs)的积累,伴随着脂肪细胞的形态变化,导致这些细胞的结构刚度逐渐增加。细胞结构刚度的增加可能会影响负重脂肪组织中相邻脂肪细胞的局部变形,根据先前的研究,这可能会加速细胞质内脂质的产生,从而形成更大且堆积更紧密的细胞内脂滴。这个过程基于机械转导现象,据推测(同样是根据实证研究),在“整体”脂肪细胞肥大中起关键作用,因此通过计算建模来表征这一过程很重要。因此,我们在这里使用一组嵌入细胞外基质的脂肪细胞有限元模型,研究成熟脂肪细胞如何影响作用于相邻未成熟细胞的局部负荷。当构建体受到外部加载时,发现脂肪细胞质膜(PM)处的峰值应变能密度取决于相邻细胞中的脂质积累水平,前提是外部压缩和剪切变形足够大(分别为[公式:见原文]和[公式:见原文])。机械信号通过质膜转导,因此可能影响细胞内途径以产生更多脂质含量。我们的结果支持脂肪细胞中变形诱导分化的理论。因此,这些发现在久坐不动的生活方式背景下具有相关性,在这种生活方式中,负重脂肪组织的持续变形可能会激活一个正反馈回路,促进细胞的“整体”分化,进而增加活脂肪组织的总质量。