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Characterization of the mechanical properties of cancer cells in 3D matrices in response to collagen concentration and cytoskeletal inhibitors.

ABSTRACT: Cellular processes, such as cell migration, adhesion, and proliferation depend on the interaction between the intracellular environment and the extracellular matrix (ECM). While many studies have explored the role of the microenvironment on cell behavior, the influence of 3D matrix mechanics on intracellular activity is not completely understood. To characterize the relationship between the mechanical components of the microenvironment and intracellular behavior, we use particle-tracking microrheology of metastatic breast cancer cells embedded in 3D collagen gels to quantify the intracellular activity from which the molecular motor activity and stiffness can be determined. Our results show that increasing collagen concentration of the 3D environments leads to an increase in intracellular stiffness and motor activity. Furthermore, our studies demonstrate that intracellular fluctuations depend on collagen concentration, even in the presence of a number of frontline chemotherapeutic and anti-MMP drugs, indicating that ECM concentration is an important and indispensable parameter to consider in drug screening.

SUBMITTER: Kim JE

PROVIDER: S-EPMC5916796 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Characterization of the mechanical properties of cancer cells in 3D matrices in response to collagen concentration and cytoskeletal inhibitors.

Kim Jessica E JE Reynolds Daniel S DS Zaman Muhammad H MH Mak Michael M

Integrative biology : quantitative biosciences from nano to macro 20180401 4

Cellular processes, such as cell migration, adhesion, and proliferation depend on the interaction between the intracellular environment and the extracellular matrix (ECM). While many studies have explored the role of the microenvironment on cell behavior, the influence of 3D matrix mechanics on intracellular activity is not completely understood. To characterize the relationship between the mechanical components of the microenvironment and intracellular behavior, we use particle-tracking microrh ...[more]

PMID: 29620778

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Project description:In the tumor microenvironment (TME), collagen fibers facilitate tumor cell migration through the extracellular matrix. Previous studies have focused on studying the responses of cells on uniformly aligned or randomly aligned collagen fibers. However, the in vivo environment also features spatial gradients in alignment, which arise from the local reorganization of the matrix architecture due to cell-induced traction forces. Although there has been extensive research on how cells respond to graded biophysical cues, such as stiffness, porosity, and ligand density, the cellular responses to physiological fiber alignment gradients have been largely unexplored. This is due, in part, to a lack of robust experimental techniques to create controlled alignment gradients in natural materials. In this study, we image tumor biopsy samples and characterize the alignment gradients present in the TME. To replicate physiological gradients, we introduce a first-of-its-kind biofabrication technique that utilizes a microfluidic channel with constricting and expanding geometry to engineer 3D collagen hydrogels with tunable fiber alignment gradients that range from sub-millimeter to millimeter length scales. Our modular approach allows easy access to the microengineered gradient gels, and we demonstrate that HUVECs migrate in response to the fiber architecture. We provide preliminary evidence suggesting that MDA-MB-231 cell aggregates, patterned onto a specific location on the alignment gradient, exhibit preferential migration towards increasing alignment. This finding suggests that alignment gradients could serve as an additional taxis cue in the ECM. Importantly, our study represents the first successful engineering of continuous gradients of fiber alignment in soft, natural materials. We anticipate that our user-friendly platform, which needs no specialized equipment, will offer new experimental capabilities to study the impact of fiber-based contact guidance on directed cell migration.

Dataset Information

Characterization of the mechanical properties of cancer cells in 3D matrices in response to collagen concentration and cytoskeletal inhibitors.

Publications

Characterization of the mechanical properties of cancer cells in 3D matrices in response to collagen concentration and cytoskeletal inhibitors.

Similar Datasets

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