Simultaneous generation of chemical concentration and mechanical shear stress gradients using microfluidic osmotic flow comparable to interstitial flow.
Cells are very sensitive to various microenvironmental cues, including mechanical stress and chemical gradients. Therefore, physiologically relevant models of cells should consider how cells sense and respond to microenvironmental cues. This can be accomplished by using microfluidic systems, in which fluid physics can be realized at a nanoliter scale. Here we describe a simple and versatile method to study the generation of chemical concentration and mechanical shear stress gradients in a single microfluidic chip. Our system uses an osmotic pump that produces very slow (<a few microm/s) and controlled flow, allowing a wide and stable diffusion of specific chemical concentration. We also established a shear stress gradient passively via a circular channel in the interstitial level. For evaluation of the system, we used L929 mouse fibroblast cells and simultaneously exposed them to a mechanical stress gradient and a chemical nutrient gradient. The interstitial shear stress level clearly affected cell alignment, mobility velocity, and attachment. At the same time, cell proliferation reflected nutrient concentration level. Our system, which enables continuous and long-term culture of cells in a combined chemical and mechanical gradient, provides physiologically realistic conditions and will be applicable to studies of cancer metastasis and stem cell differentiation.
Park
Joong Yull
JY
Department of Biomedical Engineering, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea. dbiomed@korea.ac.kr
Yoo
Sung Ju
SJ
Hwang
Chang Mo
CM
Lee
Sang-Hoon
SH
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003470:Culture Media; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008954:Models, Biological; D009997:Osmotic Pressure; D033081:Shear Strength; D013314:Stress, Mechanical
D003470:Culture Media