Shoham Naama, Mor-Yossef Moldovan Lisa, Benayahu Dafna, Gefen Amit
1 Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University , Tel Aviv, Israel .
Tissue Eng Part A. 2015 Apr;21(7-8):1354-63. doi: 10.1089/ten.TEA.2014.0505. Epub 2015 Jan 19.
Mechanotransduction plays a role in adipose tissues by transducing the environmental mechanical signals. It is recognized that dynamic or cyclic mechanical strains suppress adipogenesis, but static strains activate the adipogenic signaling pathways. This phenomenon needs to be investigated further, given its potential use in tissue engineering of fat. We used in vitro cultures as model systems for studying differentiation and function of adipocytes. Additionally, using the finite element method, we developed here sets of multiscale models (MSM), which represent single or multiple adipocytes embedded in scaffolds, stimulated mechanically in a static regime. Based on in vitro adipocyte culture work, these models were employed to study the hypothesis that the loading state of the plasma membrane (PM) in adipocytes is influenced by neighboring cells, which could reflect positive feedback loops of en mass adipose cell differentiation. We demonstrate that under static loading, tensile strains at the PM increase with the stage of cell maturation. Furthermore, when the cell density was sufficient (above 19 cells per 100 μm(3)), progressive differentiation in some of the cells caused higher magnitudes of tensile strains in the PMs of other nearby cells. MSM are currently the only feasible means to correlate continuum (macrolevel) construct deformations to subcellular-level PM stretches in distorted cells. These macro-to-micro mechanobiology relationships, revealed through MSM, point to stimulations that promote the formation of lipid droplet accumulations and the increase of adipogenesis. Such models are a cost-effective useful platform for achieving better understanding of these deformation-driven cell processes toward optimized design of tissue-engineered fat constructs.
机械转导通过转换环境机械信号在脂肪组织中发挥作用。人们认识到动态或循环机械应变会抑制脂肪生成，但静态应变会激活脂肪生成信号通路。鉴于其在脂肪组织工程中的潜在应用，这一现象需要进一步研究。我们使用体外培养作为研究脂肪细胞分化和功能的模型系统。此外，我们利用有限元方法开发了多尺度模型集（MSM），该模型集代表嵌入支架中的单个或多个脂肪细胞，并在静态条件下进行机械刺激。基于体外脂肪细胞培养工作，这些模型被用于研究以下假设：脂肪细胞中质膜（PM）的负载状态受邻近细胞影响，这可能反映了大量脂肪细胞分化的正反馈回路。我们证明，在静态加载下，质膜处的拉伸应变随着细胞成熟阶段而增加。此外，当细胞密度足够时（每100 μm(3)超过19个细胞），一些细胞的渐进分化会导致其他附近细胞质膜中更高程度的拉伸应变。多尺度模型目前是将连续体（宏观水平）结构变形与扭曲细胞中亚细胞水平质膜拉伸相关联的唯一可行方法。通过多尺度模型揭示的这些宏观到微观的力学生物学关系，指出了促进脂滴积累形成和脂肪生成增加的刺激因素。此类模型是一个具有成本效益的有用平台，有助于更好地理解这些由变形驱动的细胞过程，从而优化组织工程脂肪构建体的设计。
