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.cell mechanics | cell stiffness | biophysics | suspended microchannel resonator | biosensors

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

“…S1E) when cells were in a suspended state, as measured by PMF. Alternatively, it is possible that retention might increase due to cell-surface interactions (Byun et al, 2013), for example if βAR activation changes the surface properties of cancer cells to modulate electrostatic and van der Waals interactions between cells and the porous membrane. However, we determined that there was no significant difference between the adhesion of vehicle-and isoproterenol-treated cells to a silicon nitride atomic force microscope tip (Fig.…”

Systematic Analysis of the Functional Relevance of Nuclear Structure and Mechanics in Breast Cancer Progression

“…Our preliminary experiments on MDA-MB-231 cells revealed that cells with reduced expression of lamins A/C were able to pass through the 5µm constrictions significantly faster than comparably sized cells with normal levels of lamins A and C (mock controls). As cell size varied between the various populations and it was recently shown that the transit time of cells through narrow constriction exponentially increases with cell size, 6 we also plotted the regression curves for MDA-MB-231 cells with reduced levels of lamin A/C and mock controls (Fig. 2).…”

High‐throughput linear optical stretcher for mechanical characterization of blood cells

“…One approach is the microfluidic cell deformability cytometer which are inexpensive to prototype, use small sample volumes (nanoliters), and employ laminar flow characteristics (24) allowing for predictable and controllable flow. For example, physical constrictions (25)(26)(27)(28) or inertial focusing flow (29)(30)(31) have been used to create contact or shear forces (> 1 nN (30)) capable of significantly deforming flowing cells. Large strains (>10% deformation) however, can damage cells and should be avoided when cell isolation and viability post-analysis are of interest.…”