Department of Physics, Technische Universität München and Graduate School of Quantitative Biosciences, Ludwig-Maximilians-Universität München, James-Franck-Str. 1, 85748, Garching, Germany.
Dipartimento di Matematica, Sapienza Università di Roma, P.le A. Moro 5, 00185, Rome, Italy.
Sci Rep. 2017 Oct 6;7(1):12737. doi: 10.1038/s41598-017-13070-3.
In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from 'wild type' donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative confirmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems.
在本文中，我们讨论了数值描述符和统计物理概念在通过器官芯片方法观察微观水平的复杂生物系统时的适用性。为此，我们利用在微流控平台上收集的数据，白细胞可以通过适当构建的通道向其目标移动。白细胞的行为通过标准的时移成像记录。特别是，我们分析了三组人外周血单核细胞（PBMC）：杂合突变体（其中只有一个 FPR1 基因的副本正常）、纯合突变体（其中编码 FPR1 的两个等位基因都是功能丧失变体）和来自“野生型”供体的细胞（FPR1 正常表达）。我们对这些细胞的迁移进行了特征描述，定量证实了 FPR1 在癌症化疗反应中的重要作用。事实上，野生型 PBMC 会向接受化疗的癌细胞进行有偏差的随机游走，并与它们建立持久的相互作用。相反，杂合突变体在其运动中表现出较弱的偏差，而纯合突变体则表现出相当不相关的随机游走，两者都无法与它们的目标接触。接下来，我们关注野生型细胞，并研究白细胞与癌细胞的相互作用，提出了一种新的启发式方法，该方法受动力系统中 Lyapunov 稳定性的启发。
