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Glioblastoma (GB) is the most common and most aggressive form of primary brain t

ID: 218914 • Letter: G

Question

Glioblastoma (GB) is the most common and most aggressive form of primary brain tumor. Concentrations of extracellular matrix proteins, such as collagen and hyaluronic acid, are elevated in brain tumor microenvironments, which increases tissue stiffness. For example, normal brain has an elastic modulus of 1 kPa and GB tissue has an elastic modulus of 30 kPa. These changes in the mechanical properties of the extracellular matrix are thought to stimulate tumor cell proliferation.

Suppose you want to measure the proliferation of GB tumor cells as a function of extracellular matrix stiffness. You decide to use cross-linked Alginate hydrogels to mimic healthy brain and brain tumor microenvironments. To tune the elastic modulus, you make hydrogels with increasing concentrations of Calcium and measure their stress-strain curves. The results are below. Based on these results, which concentration would you choose to mimic a healthy brain? Which concentration would you choose to mimic a GB tumor? Briefly justify your choices.

150 120 a 90 ? ?? 1 . : 20% ? ? ¡- | 16%, : 890 O 60 30 | 4% 0 0 1 2 3 4 5 Strain

Explanation / Answer

Glioblastoma is a tumor of astrocytes in the brain. Astrocytes are star-shaped glue like cells that serve as supportive tissue in the brain. Glioblastoma is highly malignant tumor due to its rich supply of blood vessels and high proliferation rate. In Glioblastoma, tissue stiffness is increased due to the secretion of collagen and hyaluronic acid.

Given information,

The elastic modulus of normal brain = 1 kPa

The elastic modulus of Glioblastoma = 30 kPa

For simulating normal brain conditions, 2% alginate hydrogen can be used.

For 2% gel,

Elastic modulus = Stress/Strain = 5/5 = 1 kPa

For simulating Glioblastoma conditions, 16% alginate hydrogen can be used.

For 16% gel,

Elastic modulus = Stress/Strain = 150/5 = 30 kPa

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