Controlling Embryonic Cell Sheet Migration Using Microfluidics
Melis Hazar (Carnegie Mellon university), YongTae Kim (Koch Institute for Integrative Cancer Research Massachusetts Institute of Tech), Lance Davidson (Departments of Bioengineering and Developmental Biology University of Pittsburgh), Philip LeDuc (Carnegie Mellon University), William Messner (Tufts University)
Mechanics of cell sheets, multicellular assemblies and tissues
Mon 9:00 - 10:30
Barus-Holley 141
Embryonic development consists of a complex series of cell signaling, cell migration and cell differentiation events whereas morphogenesis is the process that controls the organized spatiotemporal distributions of these events. Cell sheet migration is central to embryonic development, to homeostasis of complex organs, and to disease pathology therefore studying cell migration within sheets is important. Embryos from the African Claw-toed frog, Xenopus laevis, are used to elucidate genes important in moving cells. However, little is known about the underlying mechanism by which cells in epithelial sheets coordinate their responses to growth factors, directional signals, and motility cues to direct sheet movement in vivo. One reason for this knowledge gap is the lack of technologies to control of the chemical microenvironment surrounding multicellular tissues. Here, we manipulate the chemical microenvironment with precise spatiotemporal delivery of cytoskeletal inhibitors and contraction-stimulating compounds using laminar flow interfaces with microfluidics. We find that microfluidics can pattern cell responses and control motility of multicellular sheets and may allow engineers the ability to initiate and control the outcome of synthetic morphogenetic programs. To deliver precise chemical stimulation to a multicellular tissue, we have developed a system for controlling the inlet pressures to a microfluidic device by modulating fluidic resistance and capacitance. We employed this system to deliver chemicals over tissue explants from Xenopus embryos with a spatiotemporal control to study mechanical patterning and local control of cell sheet migration during epibolic-type morphogenetic movements. We believe that the ability to control the form of multicellular tissues potentially has high impact in tissue engineering and regeneration applications in bioengineering and medicine.