Dataset Information

Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns.

ABSTRACT: Various subcellular activities, such as protrusion and detachment, compose a cell migration process. The molecular mechanisms of these subcellular activities have been elucidated. However, there is no method that can assess the contributions of these subcellular activities to the global cell migration pattern of a given cell type. Hence, we develop a powerful approach based on CN correlations that quantitatively profiles the cell migration pattern of a given cell type in terms of assembled subcellular activities. In this way, we bridge migration data at the cellular level with underlying molecular mechanisms. The CN correlation profile is found to uniquely and consistently represent the cell migration pattern of each cell type probed. It can clearly reveal the effects of molecular perturbations, such as Y27632 and Cdc42 knockdown on each subcellular migratory activity. As a result, the CN correlation approach serves as a cell dynamic descriptor that can extract comprehensive quantitative data from cell migration movies for integrative biological analyses.

SUBMITTER: Lan T

PROVIDER: S-EPMC5784082 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns.

Lan Tian T Hung Shen-Hsiu SH Su Xudong X Wong Samuel W K SWK Tseng Yiider Y

Scientific reports 20180124 1

Various subcellular activities, such as protrusion and detachment, compose a cell migration process. The molecular mechanisms of these subcellular activities have been elucidated. However, there is no method that can assess the contributions of these subcellular activities to the global cell migration pattern of a given cell type. Hence, we develop a powerful approach based on CN correlations that quantitatively profiles the cell migration pattern of a given cell type in terms of assembled subce ...[more]

PMID: 29367613

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Project description:In mesenchymal cell motility, several migration patterns have been observed, including directional, exploratory and stationary. Two key members of the Rho-family of GTPases, Rac and Rho, along with an adaptor protein called paxillin, have been particularly implicated in the formation of such migration patterns and in regulating adhesion dynamics. Together, they form a key regulatory network that involves the mutual inhibition exerted by Rac and Rho on each other and the promotion of Rac activation by phosphorylated paxillin. Although this interaction is sufficient in generating wave-pinning that underscores cellular polarization comprised of cellular front (high active Rac) and back (high active Rho), it remains unclear how they interact collectively to induce other modes of migration detected in Chinese hamster Ovary (CHO-K1) cells. We previously developed a six-variable (6V) reaction-diffusion model describing the interactions of these three proteins (in their active/phosphorylated and inactive/unphosphorylated forms) along with other auxiliary proteins, to decipher their role in generating wave-pinning. In this study, we explored, through computational modeling and image analysis, how differences in timescales within this molecular network can potentially produce the migration patterns in CHO-K1 cells and how switching between migration modes could occur. To do so, the 6V model was reduced to an excitable 4V spatiotemporal model possessing three different timescales. The model produced not only wave-pinning in the presence of diffusion, but also mixed-mode oscillations (MMOs) and relaxation oscillations (ROs). Implementing the model using the Cellular Potts Model (CPM) produced outcomes in which protrusions in the cell membrane changed Rac-Rho localization, resulting in membrane oscillations and fast directionality variations similar to those observed experimentally in CHO-K1 cells. The latter was assessed by comparing the migration patterns of experimental with CPM cells using four metrics: instantaneous cell speed, exponent of mean-square displacement ([Formula: see text]-value), directionality ratio and protrusion rate. Variations in migration patterns induced by mutating paxillin's serine 273 residue were also captured by the model and detected by a machine classifier, revealing that this mutation alters the dynamics of the system from MMOs to ROs or nonoscillatory behaviour through variation in the scaled concentration of an active form of an adhesion protein called p21-Activated Kinase 1 (PAK). These results thus suggest that MMOs and adhesion dynamics are the key mechanisms regulating CHO-K1 cell motility.

Dataset Information

Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns.

Publications

Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns.

Similar Datasets

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