Hierarchical Collagen Nanofiber Gels Recapitulate a Physiologically Relevant Tumor Stromal Microenvironment

Area of Science:

• Biomaterials Science
• Cancer Biology
• Tissue Engineering

Background:

• Cancer stroma stiffens due to increased type I collagen (Col I) production and cross-linking.
• This stiffened stroma exerts mechanical stress on cancer cells, promoting tumor progression.
• There is a need for culture scaffolds that replicate the tumor stromal microenvironment's characteristics.

Purpose of the Study:

• To create a scaffold material mimicking the fibrous structure and elastic modulus of in vivo cancer tissue using Col I.
• To evaluate the suitability of these scaffolds for culturing cancer cells and studying cancer cell-matrix interactions.

Main Methods:

• Fabrication of collagen gels with varying concentrations of collagen microfibers (CMFs) and collagen nanofibers (CNFs).
• Measurement of elastic moduli of the fabricated collagen gels.
• Culture of JC-011 cancer cells on CNF gels with elasticity similar to colorectal cancer tissue and comparison with Matrigel culture.

Main Results:

• Collagen gels with elastic moduli ranging from 1 to 18 kPa (CMFs) and 2 to 80 kPa (CNFs) were produced.
• JC-011 cells cultured on CNF gels showed proliferation comparable to Matrigel.
• Cancer-related protein expression in JC-011 cells on CNF gels closely resembled that on Matrigel.

Conclusions:

• Hierarchical CNF gels effectively recapitulate a physiologically relevant tumor stromal microenvironment.
• These collagen-based scaffolds offer a promising platform for investigating cancer cell-matrix interactions.
• The developed scaffolds can aid in understanding cancer progression mechanisms within the tumor microenvironment.