Dataset Information

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

ABSTRACT: Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters on the tumor, and its potential use as a biomarker using a hyaluronic acid hydrogel system capable of elastic modulus tuning and dynamic elastic moduli changes. Experiments were conducted to assess the sensitivity of glioblastoma cell populations with different mutations to varying elastic moduli. Cells with aberrant epithelial growth factor receptor (EGFR) expression have a predilection for a stiffer environment, sensing these parameters through focal adhesion kinase (FAK). Importantly, the inhibition of FAK or EGFR generally resulted in reversed elastic modulus preference. Lastly, we explore the concept of therapeutically targeting the elastic modulus and dynamically reducing it via chemical or enzymatic degradation, both showing the capability to reduce or stunt proliferation rates of these GBM populations.

SUBMITTER: Sivakumar H

PROVIDER: S-EPMC6318698 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Sivakumar Hemamylammal H Strowd Roy R Skardal Aleksander A

Gels (Basel, Switzerland) 20170713 3

Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters ...[more]

PMID: 30920523

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Project description:In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. STATEMENT OF SIGNIFICANCE: Accurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.

Dataset Information

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Publications

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Similar Datasets

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