Abstract
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.
Highlights
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
Inspection of the latter allows a qualitative description of the environment: if both eigenvalues are negative, the peripheral blood mononuclear cells (PBMC) are going to engage a stable interaction with the tumor cells (TC); if their signs disagree, the PBMCs are partly attracted by the TC but not as much as required to steadily remain around it; if both the eigenvalues are positive, the PBMCs would be repelled by the tumor cell and move away: checking these possible outcomes in our OOC experiment is a routine that we perform extensively over the whole data-set, where we find robust evidence for attractive and partly attractive behaviors
Immune cells work as probes to explore their surroundings and we aim to reconstruct the chemo-attractive landscape that tumor cells generate by inspecting how PBMCs walk in this landscape
Summary
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. The rationale of the experiments was to study the interaction between human cancer cells (breast and colon), which were treated with chemotherapeutic agents, and human peripheral blood mononuclear cells (PBMC), which carried different genetic variants of the FPR1 gene. The experiments analyzed in this paper were performed in microfluidic platforms (see Fig. 1) and show the interaction between breast cancer cells and PBMC cells obtained from healthy donors bearing the FPR1 allele in homozygosis (CC), the RS867228 loss of function allele of FPR1 in heterozygosis (CA) and the RS867228 loss of function allele of FPR1 in homozygosis (AA)
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