title: Flow and diffusion in channel-guided cell migration.
abstract: Collective migration of mechanically coupled cell layers is a notable feature of wound healing, embryonic development, and cancer progression. In confluent epithelial sheets, the dynamics have been found to be highly heterogeneous, exhibiting spontaneous formation of swirls, long-range correlations, and glass-like dynamic arrest as a function of cell density. In contrast, the flow-like properties of one-sided cell-sheet expansion in confining geometries are not well understood. Here, we studied the short- and long-term flow of Madin-Darby canine kidney (MDCK) cells as they moved through microchannels. Using single-cell tracking and particle image velocimetry (PIV), we found that a defined averaged stationary cell current emerged that exhibited a velocity gradient in the direction of migration and a plug-flow-like profile across the advancing sheet. The observed flow velocity can be decomposed into a constant term of directed cell migration and a diffusion-like contribution that increases with density gradient. The diffusive component is consistent with the cell-density profile and front propagation speed predicted by the Fisher-Kolmogorov equation. To connect diffusion-mediated transport to underlying cellular motility, we studied single-cell trajectories and occurrence of vorticity. We discovered that the directed large-scale cell flow altered fluctuations in cellular motion at short length scales: vorticity maps showed a reduced frequency of swirl formation in channel flow compared with resting sheets of equal cell density. Furthermore, under flow, single-cell trajectories showed persistent long-range, random-walk behavior superimposed on drift, whereas cells in resting tissue did not show significant displacements with respect to neighboring cells. Our work thus suggests that active cell migration manifests itself in an underlying, spatially uniform drift as well as in randomized bursts of short-range correlated motion that lead to a diffusion-mediated transport.
authors.affiliation: Fakultät für Physik, Ludwig Maximilians Universität, München, Germany; Center for NanoScience, Ludwig Maximilians Universität, München, Germany; Nanosystems Initiative Munich, München, Germany.
authors.forename: Anna-Kristina
authors.initials: AK
authors.lastname: Marel
authors.affiliation: Fakultät für Physik, Ludwig Maximilians Universität, München, Germany; Center for NanoScience, Ludwig Maximilians Universität, München, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zorn
authors.affiliation: Fakultät für Physik, Ludwig Maximilians Universität, München, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klingner
authors.affiliation: Institute of Cell Dynamics and Imaging, University of Münster, Münster, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Wedlich-Söldner
authors.affiliation: Fakultät für Physik, Ludwig Maximilians Universität, München, Germany; Center for NanoScience, Ludwig Maximilians Universität, München, Germany; Arnold Sommerfeld Center, Ludwig Maximilians Universität, München, Germany; Nanosystems Initiative Munich, München, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Frey
authors.affiliation: Fakultät für Physik, Ludwig Maximilians Universität, München, Germany; Center for NanoScience, Ludwig Maximilians Universität, München, Germany; Nanosystems Initiative Munich, München, Germany. Electronic address: raedler@lmu.de.
authors.forename: Joachim O
authors.initials: JO
authors.lastname: Rädler
mesh_terms: D000818:Animals; D002465:Cell Movement; D004058:Diffusion; D004285:Dogs; D061985:Madin Darby Canine Kidney Cells; D008689:Methacrylates; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008954:Models, Biological; D061848:Optical Imaging; D011092:Polyethylene Glycols; D012399:Rotation; D059010:Single-Cell Analysis / Q000295:instrumentation / Q000379:methods; D014741:Video Recording
chemical_list: D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols