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Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

ABSTRACT: Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-making. Energetic costs, driven by the cellular work needed to generate force for matrix displacement, increase with increasing cell stiffness, matrix stiffness, and degree of spatial confinement, limiting migration. By assessing energetic costs between possible migration paths, we can predict the probability of migration choice. Our findings indicate that motility in confined spaces imposes high energetic demands on migrating cells, and cells migrate in the direction of least confinement to minimize energetic costs. Therefore, therapeutically targeting metabolism may limit cancer cell migration and metastasis.

SUBMITTER: Zanotelli MR

PROVIDER: S-EPMC6744572 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

Zanotelli Matthew R MR Rahman-Zaman Aniqua A VanderBurgh Jacob A JA Taufalele Paul V PV Jain Aadhar A Erickson David D Bordeleau Francois F Reinhart-King Cynthia A CA

Nature communications 20190913 1

Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-maki ...[more]

PMID: 31519914

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Project description:BACKGROUND:Some studies, mainly coming from the U.S., indicate disparities in heart failure (HF) treatment according to migration/ethnicity. However, respective results are inconsistent and cannot be transferred to other health care systems. Thus, we will address the following research question: Are there differences in the diagnosis and management of HF between patients with and without a Turkish migration background in Germany? METHODS:A factorial experimental design with video vignettes was applied. In the filmed simulated initial encounters, professional actors played patients, who consulted a primary care physician because of typical HF symptoms. While the dialog was identical in all videos, patients differed in terms of Turkish migration history (no/yes), sex (male/female), and age (55?years/75?years). After viewing the video, primary care physicians (N =?128) were asked standardized and open ended questions concerning their decisions on diagnosis and therapy. RESULTS:Analyses revealed no statistically significant differences (p <?0.05), but a consistent tendency: Primary care doctors more often asked lifestyle and psychosocial questions, they more often diagnosed HF, they gave more advice to rest and how to behave in case of deterioration, they more often auscultated the lung, and more often referred to a specialist when the patient has a Turkish migration history compared to a non-migrant patient. Differences in the medical decisions between the two groups ranged between 1.6 and 15.8%. In 10 out of 12 comparisons, differences were below 10%. CONCLUSIONS:Our results indicate that are no significant inequalities in diagnosis and management of HF according to a Turkish migration background in Germany. Primary care physicians' behaviour and medical decision making do not seem to be influenced by the migration background of the patients. Future studies are needed to verify this result and to address inequalities in HF therapy in an advanced disease stage.

Dataset Information

Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

Publications

Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

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