A Programmable Multifunctional 3D Cancer Cell Invasion Micro Platform

Small, vol. 18, pp. e2107757

Abstract

In the research of cancer cell invasion and metastasis, recreation of physiologically relevant and faithful three-dimensional (3D) tumor models that recapitulate spatial architecture, spatiotemporal control of cell communication and signaling pathways, and integration of extracellular cues remains an open challenge. Here, a programmable multifunctional 3D cancer cell invasion microbuckets-hydrogel (Mb-H) platform is developed by integrating various function-variable microbuckets and extracellular matrix (ECM)-like hydrogels. Based on this Mb-H micro platform, the aggregation of multi-cancer cells is well controlled to form cancer cell spheroids, and the guiding relationship of single-cell migration and collective cell migration during the epithelial-mesenchymal transition (EMT) of cancer cell invasion are demonstrated. By programming and precisely assembling multiple functions in one system, the Mb-H platform with spatial-temporal controlled release of cytokine transforming growth factor beta (TGF-β) and various functionalized Mb-H platforms with intelligent adjustment of cell-matrix interactions are engineered to coordinate the 3D invasive migration of cancer cell spheroids. This programmable and adaptable 3D cancer cell invasion micro platform takes a new step toward mimicking the dynamically changing (localized) tumor microenvironment and exhibits wide potential applications in cancer research, bio-fabrication, cell signaling, and drug screening.

Authors 6

1. Qian Liu corresponding

   Guangzhou Laboratory · Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 Delft 2629 HZ The Netherlands

   Guangzhou Laboratory XingDaoHuanBei Road 9, Guangzhou International Bio Island Guangzhou Guangdong Province 510005 P. R. China

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, Delft, 2629 HZ The Netherlands

   Guangzhou Laboratory, XingDaoHuanBei Road 9, Guangzhou International Bio Island, Guangzhou, Guangdong Province, 510005 P. R. China

2. Aswin Muralidharan

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 Delft 2629 HZ The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, Delft, 2629 HZ The Netherlands

3. Abtin Saateh

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 Delft 2629 HZ The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, Delft, 2629 HZ The Netherlands

4. Zhaoying Ding

   Delft University of Technology

   Affiliation as printed

   Department of Materials Science and Engineering Delft University of Technology Mekelweg 2 Delft 2628 CD The Netherlands

   Department of Materials Science and Engineering, Delft University of Technology, Mekelweg 2, Delft, 2628 CD The Netherlands

5. Peter ten Dijke Aachen Department of Cell and Chemical Biology and Oncode Institute

   Leiden University Medical Center

   Affiliation as printed

   Department of Cell and Chemical Biology and Oncode Institute Leiden University Medical Center Einthovenweg 20 Leiden 2333 ZC The Netherlands

   Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Einthovenweg 20, Leiden, 2333 ZC The Netherlands

6. Pouyan E. Boukany corresponding

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 Delft 2629 HZ The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, Delft, 2629 HZ The Netherlands