影响乳腺癌侵入脂肪组织的物理特征的计算建模
Computational modeling of the physical features that influence breast cancer invasion into adipose tissue
AI总结：
本文通过活跃内聚球形癌细胞侵入可变形多面体脂肪细胞的计算模拟，提出无量纲能量尺度 $E_c$ 作为侵入判据，并揭示 ECM 约束和脂肪组织空间异质性对侵入的抑制作用。
摘要：
乳腺癌向脂肪组织的侵入强烈影响疾病进展和转移。癌细胞侵入脂肪组织的程度取决于癌细胞、脂肪细胞以及脂肪组织其他关键组分的众多生化和物理特性。我们将乳腺癌侵入脂肪组织建模为一个物理过程，通过模拟活跃的、具有内聚性的球形粒子（癌细胞）侵入可变形多面体（脂肪细胞）的汇合堆积来进行研究。我们通过计算癌细胞与脂肪细胞之间的界面面积 $A_t$ 来量化侵入程度。我们确定了 $A_t$ 的长时间值随癌细胞活性与内聚强度、脂肪细胞的力学性质以及脂肪细胞所嵌入的细胞外基质（ECM）力学性质的变化关系。我们表明，将侵入程度相对于一个无量纲能量尺度 $E_c$ 作图时，数据会塌缩到一条主曲线上；$E_c$ 随癌细胞速度的均方涨落和持续时间的乘积线性增长，与系统压力成反比，并具有一个随癌细胞内聚能增大而增大的偏移量。条件 $E_c \gg 1$ 表明癌细胞将侵入脂肪组织，而当 $E_c \ll 1$ 时，癌细胞与脂肪细胞保持分离状态。我们还表明，与无约束脂肪细胞相比，ECM 对脂肪细胞位置的约束会降低 $A_t$。最后，在存在 ECM 的情况下，脂肪细胞结构和力学性质的空间异质性相对于性质均匀的脂肪组织会阻碍侵入。
英文摘要：
Breast cancer invasion into adipose tissue strongly influences disease progression and metastasis. The degree of cancer cell invasion into adipose tissue depends on numerous biochemical and physical properties of cancer cells, adipocytes, and other key components of adipose tissue. We model breast cancer invasion into adipose tissue as a physical process by carrying out simulations of active, cohesive spherical particles (cancer cells) invading into confluent packings of deformable polyhedra (adipocytes). We quantify the degree of invasion by calculating the interfacial area $A_t$ between cancer cells and adipocytes. We determine the long-time value of $A_t$ versus the activity and strength of the cohesion between cancer cells, as well as mechanical properties of the adipocytes and extracellular matrix (ECM) in which the adipocytes are embedded. We show that the degree of invasion collapses onto a master curve by plotting it versus a dimensionless energy scale $E_c$, which grows linearly with mean-square fluctuations and persistence time of the cancer cell velocities, is inversely proportional to the pressure of the system, and has an offset that increases with the cancer cell cohesive energy. The condition, $E_c \gg 1$, indicates that cancer cells will invade the adipose tissue, whereas for $E_c \ll 1$, the cancer cells and adipocytes remain demixed. We also show that constraints on adipocyte positions by the ECM decrease $A_t$ relative to that obtained for unconstrained adipocytes. Finally, spatial heterogeneity in structural and mechanical properties of the adipocytes in the presence of ECM impedes invasion relative to adipose tissue with uniform properties.
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