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Characterization of 3D matrix conditions for cancer cell migration with elasticity/porosity-independent tunable microfiber gels

Polymer Journal volume 52, pages 333–344 (2020)Cite this article

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Abstract

The mechanics and architectures of the extracellular matrix (ECM) critically influence 3D cell migration processes, such as cancer cell invasion and metastasis. Understanding the roles of mechanical and structural factors in the ECM could provide an essential basis for cancer treatment. However, it is generally difficult to independently characterize these roles due to the coupled changes in these factors in conventional ECM model systems. In this study, to solve this problem, we developed elasticity/porosity-tunable electrospun fibrous gel matrices composed of photocrosslinked gelatinous microfibers (nanometer-scale-crosslinked chemical gels) with well-regulated bonding (tens-of-micron-scale fiber-bonded gels). This system enables independent modulation of microscopic fiber elasticity and matrix porosity, i.e., the mechanical and structural conditions of the ECM. The elasticity of fibers was tuned with photocrosslinking conditions. The porosity was regulated by changing the degree of interfiber bonding. The influences of these factors of the fibrous gel matrix on the motility of MDA-MB-231 tumorigenic cells and MCF-10A nontumorigenic cells were quantitatively investigated. MDA-MB-231 cells showed the highest degree of MMP-independent invasion into the matrix composed of fibers with a Young’s modulus of 20 kPa and a low degree of interfiber bonding, while MCF-10A cells did not show invasive behavior under the same matrix conditions.

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Funding

This work was supported by a Grant-in-Aid for Scientific Research (15K12513) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and a grant for Core Research for Evolutionary Medical Science and Technology from the Japan Agency of Medical Research and Development (AMED-CREST, JP19gm0810002).

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Authors and Affiliations

  1. Graduate School of Engineering, Kyushu University, CE41-204, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan

    Daoxiang Huang, Yu Nakamura & Aya Ogata

  2. Laboratory of Biomedical and Biophysical Chemistry, Institute for Materials Chemistry and Engineering, Nishi-ku, Fukuoka, 819-0395, Japan

    Satoru Kidoaki

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  1. Daoxiang Huang
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  2. Yu Nakamura
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SK developed the idea for the study; DH, YN and AO performed the research and analyzed the data; and SK and DH wrote and revised the paper. All authors gave final approval for publication.

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Correspondence to Satoru Kidoaki.

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Huang, D., Nakamura, Y., Ogata, A. et al. Characterization of 3D matrix conditions for cancer cell migration with elasticity/porosity-independent tunable microfiber gels. Polym J 52, 333–344 (2020). https://doi.org/10.1038/s41428-019-0283-3

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