Bioconjugation of COL1 protein on liquid-like solid surfaces to study tumor invasion dynamics

Author:

Nguyen D. T.1ORCID,Pedro D. I.1ORCID,Pepe A.1ORCID,Rosa J. G.1ORCID,Bowman J. I.2ORCID,Trachsel L.2ORCID,Golde G. R.1ORCID,Suzuki I.1ORCID,Lavrador J. M.1ORCID,Nguyen N. T. Y.1ORCID,Kis M. A.1ORCID,Smolchek R. A.1ORCID,Diodati N.1ORCID,Liu R.3ORCID,Phillpot S. R.4ORCID,Webber A. R.4ORCID,Castillo P.5ORCID,Sayour E. J.35ORCID,Sumerlin B. S.2ORCID,Sawyer W. G.16ORCID

Affiliation:

1. Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, College of Medicine University of Florida 1 , Gainesville, Florida 3261

2. Department of Chemistry, College of Liberal Arts and Sciences, College of Medicine University of Florida 2 , Gainesville, Florida 3261

3. Department of Surgery, College of Medicine University of Florida 3 , Gainesville, Florida 3261

4. Department of Materials Science and Engineering Herbert Wertheim College of Engineering, College of Medicine University of Florida 4 , Gainesville, Florida 3261

5. Department of Pediatrics, College of Medicine University of Florida 5 , Gainesville, Florida 3261

6. Department of Anatomy and Cell Biology, College of Medicine University of Florida 6 , Gainesville, Florida 3261

Abstract

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

Funder

National Science Foundation

National Institutes of Health

FDOH Live Like Bella Discovery

University of Florida Health Cancer Center / University of Florida

Florida State University Clinical and Translational Science Awards

Stop Children's Cancer foundation

Publisher

American Vacuum Society

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Materials Science,Biomaterials,General Chemistry

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