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Cellular and Molecular Bioengineering

, Volume 12, Issue 1, pp 69–84 | Cite as

Degradation and Remodeling of Epitaxially Grown Collagen Fibrils

  • Juan Wang
  • Anuraag Boddupalli
  • Joseph Koelbl
  • Dong Hyun Nam
  • Xin Ge
  • Kaitlin M. Bratlie
  • Ian C. SchneiderEmail author
Article

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.

Keywords

Directed migration Second harmonic generation MT1-MMP MMP-14 Function blocking antibody 

Abbreviations

TME

Tumor microenvironment

SHG

Second harmonic generation

ECM

Extracellular matrix

TIMP

Tissue inhibitor of matrix metalloproteinase

MMP

Matrix metalloproteinase

DMEM

Dulbecco’s modified Eagles medium

FBS

Fetal bovine serum

NA

Numerical aperture

HSD

Honest significant difference

Notes

Acknowledgments

We acknowledge Zhiqi Yao and Andrew Hillier with help on the AFM imaging and Jacob Nuhn for help with the MMP assays.

Funding

This work was supported by the National Institutes of Health/National Institute for General Medical Sciences [R01GM115672]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of interest

Juan Wang, Anuraag Boddupalli, Joseph Koelbl, Dong Hyun Nam, Xin Ge, Kaitlin M. Bratlie and Ian C. Schneider state they have no conflicts of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

12195_2018_547_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1266 kb)

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Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  • Juan Wang
    • 1
  • Anuraag Boddupalli
    • 1
  • Joseph Koelbl
    • 1
  • Dong Hyun Nam
    • 2
  • Xin Ge
    • 2
  • Kaitlin M. Bratlie
    • 1
    • 3
  • Ian C. Schneider
    • 1
    • 4
    Email author
  1. 1.Department of Chemical and Biological EngineeringIowa State UniversityAmesUSA
  2. 2.Department of Chemical EngineeringUniversity of California RiversideRiversideUSA
  3. 3.Department of Materials Science and EngineeringIowa State UniversityAmesUSA
  4. 4.Department of Genetics, Development and Cell BiologyIowa State UniversityAmesUSA

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