Characterizing deformability and surface friction of cancer cells

被引:286
作者
Byun, Sangwon [1 ]
Son, Sungmin [2 ]
Amodei, Dario [7 ]
Cermak, Nathan [3 ]
Shaw, Josephine [1 ]
Kang, Joon Ho [4 ]
Hecht, Vivian C. [1 ]
Winslow, Monte M. [6 ,8 ]
Jacks, Tyler [5 ,6 ]
Mallick, Parag [7 ]
Manalis, Scott R. [1 ,2 ,3 ,6 ]
机构
[1] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
[2] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[3] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA
[4] MIT, Dept Phys, Cambridge, MA 02139 USA
[5] MIT, Dept Biol, Cambridge, MA 02139 USA
[6] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[7] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA
[8] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
关键词
cell mechanics; cell stiffness; biophysics; suspended microchannel resonator; biosensors; CIRCULATING TUMOR-CELLS; LIVING CELLS; HUMAN NEUTROPHILS; SINGLE CELLS; MECHANICS; BLOOD; ASPIRATION; ENRICHMENT;
D O I
10.1073/pnas.1218806110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7580 / 7585
页数:6
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