Microfluidic Systems For Investigating And Modulating Single-Cell Cancer Invasion Dynamics
My research entails the design and implementation of microfluidic systems to investigate the mechanical dynamics in cancer invasion at the single -cell level. Metastasis, the process of cancer spreading, is the leading cause of cancer related deaths, but the principles and dynamics that drive this process remain largely unknown. The challenge is in part due to the large spatial and temporal scales that the metastatic process spans, as it could involve single-cells transporting to distal sites across meters and over months to years. To address this challenge, my goal is to create microsystems that aim to recapitulate the critical steps in dissemination. Cell scaled microchannels with subnucleus-scaled barriers are incorporated to elucidate the mechanical transition dynamics of invasive cancer cells. Single-cell - single-barrier interactions are induced and invasive behavior is elicited. Different regulators of invasion are explored, including molecular modulators of microtubules and actomyosin as well as mechanical factors such as dimensional, directional, and other engineered spatially asymmetric cues. Results of my work have shown that microtubule stabilization suppresses cell invasion across subnucleus-scaled barriers, physiologically ubiquitous mechanical cues such as dimensionality and directionality modulate migratory cell decision making, myosin IIa activity inhibition can alter invasion patterns, and certain mechanically asymmetric microenvironments can potentially suppress dissemination via the phenomenon iteratio ad nauseam.
Microfluidics; Cancer Invasion; Single-Cell
Yen, Andrew; Zipfel, Warren R.
Ph. D., Biomedical Engineering
Doctor of Philosophy
dissertation or thesis