论文标题

细胞粘弹性的分数计算建模比整数订购模型更强大地量化药物反应和成熟

Fractional calculus modeling of cell viscoelasticity quantifies drug response and maturation more robustly than integer order models

论文作者

Vo, Anh, Ekpenyong, Andrew

论文摘要

最近已经发现,细胞的粘弹性是反映细胞的复杂生物学状态,功能和故障的固有标记。尽管使用整数机械和幂律粘弹性模型成功完成了从许多细胞类型的粘弹性数据中提取模型参数,但是在某些细胞类型和条件下,拟合的优点落后于一些细胞类型和条件。因此,已经提出了部分粘弹性模型为更一般,更适合这种建模。在这项工作中,我们使用Integer Order模型已拟合的已发布数据测试了此类普遍性。我们发现,在比整数阶的情况下,可以使用分数粘弹性模型拟合细胞粘弹性数据。对于在免疫系统中起作用的白细胞中的巨噬细胞,kelvin-voigt模型的分数最佳捕获了药理干预措施和细胞成熟。巨噬细胞的稳态粘度在F-肌动蛋白解散后使用药物细胞切拉蛋白D降低,并且在使用BLEBBISTATIN分解后,肌球蛋白II分解后也降低。当巨噬细胞用细菌衍生的趋化剂处理时,稳态粘度会降低。有趣的是,随着细胞成熟并接近衰老,稳态粘度和弹性模量都会逐渐改变。综上所述,这些结果表明,比整数订单建模更强大的分数粘弹性建模可以进一步量化细胞功能和故障,并具有潜在的诊断和治疗应用,尤其是在癌症和免疫系统功能障碍的情况下。

It has recently been discovered that the viscoelastic properties of cells are inherent markers reflecting the complex biological states, functions and malfunctions of the cells. Although the extraction of model parameters from the viscoelasticity data of many cell types has been done successfully using integer order mechanical and power-law viscoelastic models, there are some cell types and conditions where the goodness of fits falls behind. Thus, fractional order viscoelastic models have been proposed as more general and better suited for such modeling. In this work, we test such proposed generality using published data already fitted by integer order models. We find that cell viscoelasticity data can be fitted using fractional order viscoelastic models in more situations than integer order. For macrophages, which are among the white blood cells that function in the immune system, the fractional order Kelvin-Voigt model best captures pharmacological interventions and maturation of the cells. The steady state viscosity of macrophages decreases following depolymerization of F-actin using the drug cytochalasin D, and also decreases following myosin II breakdown using Blebbistatin. When macrophages are treated with a bacterium-derived chemoattractant, the steady state viscosity decreases. Interestingly, both the steady state viscosity and elastic modulus are progressively altered as the cells become mature and approach senescence. Taken together, these results show that fractional viscoelastic modeling, more robustly than integer order modeling, enables the further quantification of cell function and malfunction, with potential diagnostic and therapeutic applications especially in cases of cancer and immune system dysfunctions.

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