[Integrative Biology] A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrop
Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are 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 well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested 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 questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D2-Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.
Ke Yang,abc Jiandong Wu,c Guoqing Xu,d Dongxue Xie,ce Hagit Peretz-Soroka,c Susy Santos,fg Murray Alexander,h Ling Zhu,a Michael Zhang,i Yong Liu*a and Francis Lin*c Author affiliations * Corresponding authors a Institute of Applied Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, P. R. China b University of Science and Technology of China, Hefei, P. R. China c Department of, Physics and Astronomy, University of Manitoba, Winnipeg, Canada E-mail: firstname.lastname@example.org Tel: +1-204-474-9895 d Applied Computer Science, The University of Winnipeg, Winnipeg, Canada e Department of Genetics, Jilin University, China f Victoria General Hospital and River Heights/Fort Garry Community Areas, Winnipeg, Canada g South Winnipeg Integrated Health & Social Services, Winnipeg, Canada h Department of Physics, University of Winnipeg, Winnipeg, Canada i Seven Oaks General Hospital, Winnipeg, Canada