Directed cell migration induced by multiple cues in the engineered microenvironment

Directed cancer cell migration induced by the environmental signals is a critical process in cancer metastasis. Cancer cells are exposed to complex chemical and mechanical signals stimulating directed migration in the tumor microenvironment, where the physical nature is highly complex. It is still barely understood how cells sense and process the complex environmental signals through the complex intercellular signaling networks to execute the cell responses. This study explores the migratory response of cancer cells under a single and combined signal. The driving hypothesis is that the cell innate capability constraints the signal stimulations physically in inducing directed cell migration. We assess the hypothesis by engineering the microenvironment in the microfluidic platform, exposing a single or combined signal environment. The combined signal environment is established by 1) two different chemoattractants (TGF-β1 and EGF) and 2) the convection-driven signal environment (TGF-β1 and interstitial flow). The results show that the performance of cancer cell directed migration is physically constrained when the environmental stimulation meets the cell’s innate physical limit. We illustrate the results in a physical and quantitative manner. This approach provides a novel insight to understand the cellular process and eventually enables to predict the cellular response under the complex environmental signals.