Ambrosi D, Pezzuto S, Riccobelli D, Stylianopoulos T, Ciarletta P
MOX-Dipartimento di Matematica, Politecnico di Milano, piazza Leonardo da Vinci 32, 20133 Milano, Italy.
Universitá della Svizzera Italiana, Institute of Computational Science, Faculty of Informatics, Via Giuseppe Buffi 13, 6900 Lugano, Switzerland.
J Elast. 2017 Dec;129(1-2):107-124. doi: 10.1007/s10659-016-9619-9. Epub 2017 Jan 9.
The experimental evidence that a feedback exists between growth and stress in tumors poses challenging questions. First, the rheological properties (the "constitutive equations") of aggregates of malignant cells are still a matter of debate. Secondly, the feedback law (the "growth law") that relates stress and mitotic-apoptotic rate is far to be identified. We address these questions on the basis of a theoretical analysis of and experiments that involve the growth of tumor spheroids. We show that solid tumors exhibit several mechanical features of a poroelastic material, where the cellular component behaves like an elastic solid. When the solid component of the spheroid is loaded at the boundary, the cellular aggregate grows up to an asymptotic volume that depends on the exerted compression. Residual stress shows up when solid tumors are radially cut, highlighting a peculiar tensional pattern. By a novel numerical approach we correlate the measured opening angle and the underlying residual stress in a sphere. The features of the mechanobiological system can be explained in terms of a feedback of mechanics on the cell proliferation rate as modulated by the availability of nutrient, that is radially damped by the balance between diffusion and consumption. The volumetric growth profiles and the pattern of residual stress can be theoretically reproduced assuming a dependence of the target stress on the concentration of nutrient which is specific of the malignant tissue.
肿瘤生长与应激之间存在反馈的实验证据提出了具有挑战性的问题。首先,恶性细胞聚集体的流变特性(“本构方程”)仍是一个有争议的问题。其次,将应激与有丝分裂 - 凋亡率联系起来的反馈定律(“生长定律”)远未确定。我们基于对涉及肿瘤球体生长的实验的理论分析来解决这些问题。我们表明实体瘤表现出多孔弹性材料的几种力学特征,其中细胞成分的行为类似于弹性固体。当球体的固体成分在边界处加载时,细胞聚集体生长到一个渐近体积,该体积取决于施加的压缩力。当实体瘤被径向切割时会出现残余应力,突出了一种特殊的拉伸模式。通过一种新颖的数值方法,我们将测量的开口角度与球体中潜在的残余应力相关联。机械生物学系统的特征可以用机械力对细胞增殖率的反馈来解释,这种反馈由营养物质的可用性调节,而营养物质的可用性在扩散和消耗之间的平衡作用下沿径向衰减。假设目标应力依赖于恶性组织特有的营养物质浓度,则可以从理论上再现体积生长曲线和残余应力模式。