Campus Units

Chemical and Biological Engineering, Materials Science and Engineering, Genetics, Development and Cell Biology, Ames Laboratory

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

8-16-2018

Journal or Book Title

Cellular and Molecular Bioengineering

DOI

10.1007/s12195-018-0547-6

Abstract

Introduction: The extracellular matrix (ECM) in the tumor microenvironment contains high densities of collagen that are highly aligned, resulting in directional migration called contact guidance that facilitates efficient migration out of the tumor. Cancer cells can remodel the ECM through traction force controlled by myosin contractility or proteolytic activity controlled by matrix metalloproteinase (MMP) activity, leading to either enhanced or diminished contact guidance.

Methods: Recently, we have leveraged the ability of mica to epitaxially grow aligned collagen fibrils in order to assess contact guidance. In this article, we probe the mechanisms of remodeling of aligned collagen fibrils on mica by breast cancer cells.

Results: We show that cells that contact guide with high fidelity (MDA-MB-231 cells) exert more force on the underlying collagen fibrils than do cells that contact guide with low fidelity (MTLn3 cells). These high traction cells (MDA-MB-231 cells) remodel collagen fibrils over hours, pulling so hard that the collagen fibrils detach from the surface, effectively delaminating the entire contact guidance cue. Myosin or MMP inhibition decreases this effect. Interestingly, blocking MMP appears to increase the alignment of cells on these substrates, potentially allowing the alignment through myosin contractility to be uninhibited. Finally, amplification or dampening of contact guidance with respect to a particular collagen fibril organization is seen under different conditions.

Conclusions: Both myosin II contractility and MMP activity allow MDA-MB-231 cells to remodel and eventually destroy epitaxially grown aligned collagen fibrils.

Comments

This is a manuscript of an article published as Wang, Juan, Anuraag Boddupalli, Joseph Koelbl, Dong Hyun Nam, Xin Ge, Kaitlin M. Bratlie, and Ian C. Schneider. "Degradation and Remodeling of Epitaxially Grown Collagen Fibrils." Cellular and Molecular Bioengineering (2018). The final publication is available at Springer via DOI: 10.1007/s12195-018-0547-6. Posted with permission.

Copyright Owner

Biomedical Engineering Society

Language

en

File Format

application/pdf

Available for download on Friday, August 16, 2019

Published Version

Share

COinS