title: Characterizing deformability and surface friction of cancer cells.
abstract: Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell's passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its frictional properties with the channel wall. Here, we introduce a device that enables the precise measurement of (i) the size of a single cell, given by its buoyant mass, (ii) the velocity of the cell entering a constricted microchannel (entry velocity), and (iii) the velocity of the cell as it transits through the constriction (transit velocity). Changing the deformability of the cell by perturbing its cytoskeleton primarily alters the entry velocity, whereas changing the surface friction by immobilizing positive charges on the constriction's walls primarily alters the transit velocity, indicating that these parameters can give insight into the factors affecting the passage of each cell. When accounting for cell buoyant mass, we find that cells possessing higher metastatic potential exhibit faster entry velocities than cells with lower metastatic potential. We additionally find that some cell types with higher metastatic potential exhibit greater than expected changes in transit velocities, suggesting that not only the increased deformability but reduced friction may be a factor in enabling invasive cancer cells to efficiently squeeze through tight spaces.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sangwon
authors.initials: S
authors.lastname: Byun
authors.forename: Sungmin
authors.initials: S
authors.lastname: Son
authors.forename: Dario
authors.initials: D
authors.lastname: Amodei
authors.forename: Nathan
authors.initials: N
authors.lastname: Cermak
authors.forename: Josephine
authors.initials: J
authors.lastname: Shaw
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Kang
authors.forename: Vivian C
authors.initials: VC
authors.lastname: Hecht
authors.forename: Monte M
authors.initials: MM
authors.lastname: Winslow
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: Parag
authors.initials: P
authors.lastname: Mallick
authors.forename: Scott R
authors.initials: SR
authors.lastname: Manalis
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D048430:Cell Shape; D048429:Cell Size; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D017276:Friction; D006801:Humans; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D044085:Microfluidics; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties
chemical_list: D011092:Polyethylene Glycols
keywords: biophysics; biosensors; cell mechanics; cell stiffness; suspended microchannel resonator