Dataset Information

Dissecting Collective Cell Behavior in Polarization and Alignment on Micropatterned Substrates.

ABSTRACT: Pattern-dependent collective behaviors of cells have recently raised intensive attention. However, the underlying mechanisms that regulate these behaviors are largely elusive. Here, we report a quantitative study, combining experiment and modeling, on cell polarization and arrangement on a micropatterned substrate. We show that cells exhibit position-dependent collective behaviors that can be regulated by geometry and stiffness of the patterned substrate. We find that the driving force for these collective behaviors is the in-plane maximum shear stress in the cell layer that directs the arrangement of cells. The larger the shear stress, the more the cells preferentially align and polarize along the direction of the maximum principal stress. We also find that the aspect ratio of cell polarization shape and the degree to which cells preferentially align along the direction of maximum principal stress exhibit a biphasic dependence on substrate rigidity, corresponding to our quantitative predictions that the magnitude of the maximum shear stress is biphasically dependent on the stiffness of the substrate. As such, the driving force of these cell collective behaviors can be quantified using the maximum shear stress.

SUBMITTER: He S

PROVIDER: S-EPMC4571026 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Dissecting Collective Cell Behavior in Polarization and Alignment on Micropatterned Substrates.

He Shijie S Liu Chenglin C Li Xiaojun X Ma Shaopeng S Huo Bo B Ji Baohua B

Biophysical journal 20150801 3

Pattern-dependent collective behaviors of cells have recently raised intensive attention. However, the underlying mechanisms that regulate these behaviors are largely elusive. Here, we report a quantitative study, combining experiment and modeling, on cell polarization and arrangement on a micropatterned substrate. We show that cells exhibit position-dependent collective behaviors that can be regulated by geometry and stiffness of the patterned substrate. We find that the driving force for these ...[more]

PMID: 26244731

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Project description:Extracellular matrix stiffness has a profound effect on the behavior of many cell types. Adherent cells apply contractile forces to the material on which they adhere and sense the resistance of the material to deformation-its stiffness. This is dependent on both the elastic modulus and the thickness of the material, with the corollary that single cells are able to sense underlying stiff materials through soft hydrogel materials at low (<10 μm) thicknesses. Here, we hypothesized that cohesive colonies of cells exert more force and create more hydrogel deformation than single cells, therefore enabling them to mechanosense more deeply into underlying materials than single cells. To test this, we modulated the thickness of soft (1 kPa) elastic extracellular-matrix-functionalized polyacrylamide hydrogels adhered to glass substrates and allowed colonies of MG63 cells to form on their surfaces. Cell morphology and deformations of fluorescent fiducial-marker-labeled hydrogels were quantified by time-lapse fluorescence microscopy imaging. Single-cell spreading increased with respect to decreasing hydrogel thickness, with data fitting to an exponential model with half-maximal response at a thickness of 3.2 μm. By quantifying cell area within colonies of defined area, we similarly found that colony-cell spreading increased with decreasing hydrogel thickness but with a greater half-maximal response at 54 μm. Depth-sensing was dependent on Rho-associated protein kinase-mediated cellular contractility. Surface hydrogel deformations were significantly greater on thick hydrogels compared to thin hydrogels. In addition, deformations extended greater distances from the periphery of colonies on thick hydrogels compared to thin hydrogels. Our data suggest that by acting collectively, cells mechanosense rigid materials beneath elastic hydrogels at greater depths than individual cells. This raises the possibility that the collective action of cells in colonies or sheets may allow cells to sense structures of differing material properties at comparatively large distances.

Dataset Information

Dissecting Collective Cell Behavior in Polarization and Alignment on Micropatterned Substrates.

Publications

Dissecting Collective Cell Behavior in Polarization and Alignment on Micropatterned Substrates.

Similar Datasets

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