A dual-docking microfluidic cell migration assay (D²-Chip) for testing neutrophil chemotaxis and the memory effect

Abstract

Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health science. Neutrophil is a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the wellestablished biased random walk theory, the experimental proof was challenged by the cell's highly persistent migration nature. Special experimental design is required to test the key predictions from the random walk model. Another question that interests the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these Correspondence should be addressed to: Dr. Francis Lin, Ph.D., flin@physics.umanitoba.ca, Tel: 1-204-474-9895.

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“…Chemotactic movement, the most stated example of this migration pattern, can be found in specific types of eukaryotic cells ( Figure 1c) [33,[36][37][38]. For instance, experimental assessments indicated that the chemo-taxis of neutrophils in three-dimensional culture systems supported the predictions of the biased random walk (BRW) model for this migratory behavior [39]. The evaluation of B-cells› chemotaxis revealed that the highest chemotactic responses correspond to the medium gradient of chemokines, and thus, the autocorrelation function showed slower decrease than gentle and rigorous gradients [40].…”

“…Not applicable. The Q-Weibull Random-Walk Model Normal Epithelial and Epithelial Tumor Cells [32] Generalized Levy Walk Lymphocytes in Brain [29] Anisotropic Random-Walks Persistent Random-Walk Model Lymphocytes in Lymph Nodes [63] Hydra Cells in Cellular Communities [69] Reinforced Random-Walk Model Vascular Endothelial Cells [82] Biased Random-Walk Model Chemotactic Migration of Neutrophils [39] Bimodal Correlated Random-Walk Model Human Breast Epithelial Cells [6] Lognormal Modulated CRW T Lymphocytes [72] Persistent Random-Walk Model of Cell as a Heterogeneous Time Series Breast Tumor Cells [76] Anisotropic Persistent Random-Walk Model Fibrosarcoma [78] Stochastic Langevinequations Dictyostelium [90] Fibroblasts and Keratinocytes [92]…”

Microfluidic devices for neutrophil chemotaxis studies

“…Another type of gradient generators with three main channels are common devices for neutrophil chemotaxis studies [67][68][69][70]. The parallel side channels are usually set as the source and sink channel, which are connected to the middle gradient channel through barrier structure such as microgroove channels.…”

“…The "Microjets Device" was used to develop a method for studying gradient-induced homologous and heterologous neutrophil desensitization [68]. Recently, Yang et al [70] developed a D 2 -chip which was composed of a middle gradient channel, an outer source channel, and an outer sink channel (Fig. 3B).…”

Dynamics of Neutrophiles Phagocitary Activity after Repeated Vaccinations of Laboratory Animals by Experimental Diphtheriae Bacterial Antigen Drug

“…Це створює ймовірність того, що також будуть ідентифіковані інші клітини вродженої імунної системи з властивостями пам'яті. Ряд публікацій присвячений вивченню хіміотаксичної міграційної пам'яті нейтрофілів [22]. Представляють інтерес нещодавні дослідження про те, що менш спеціалізовані, ніж моноцити та дендритні клітини, свіжоізольовані нейтрофіли людини можуть функціонувати як антиген-презентуючі клітини пам'яті CD4 + T-клітинам in vitro та ex vivo [23].…”