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Linear and nonlinear rheology of liberase-treated breast cancer tumors.

Publication ,  Journal Article
Corder, RD; Vachieri, RB; Martin, ME; Taylor, DK; Fleming, JM; Khan, SA
Published in: Biomater Sci
March 14, 2023

Extracellular matrix (ECM) rigidity has been shown to increase the invasive properties of breast cancer cells, promoting transformation and metastasis through mechanotransduction. Reducing ECM stiffness via enzymatic digestion could be a promising approach to slowing breast cancer development by de-differentiation of breast cancer cells to less aggressive phenotypes and enhancing the effectiveness of existing chemotherapeutics via improved drug penetrance throughout the tumor. In this study, we examine the effects of injectable liberase (a blend of collagenase and thermolysin enzymes) treatments on the linear and nonlinear rheology of allograft 4T1 mouse mammary tumors. We perform two sets of in vivo mouse studies, in which either one or multiple treatment injections occur before the tumors are harvested for rheological analysis. The treatment groups in each study consist of a buffer control, free liberase enzyme in buffer, a thermoresponsive copolymer called LiquoGel (LQG) in buffer, and a combined, localized injection of LQG and liberase. All tumor samples exhibit gel-like linear rheological behavior with the elastic modulus significantly larger than the viscous modulus and both independent of frequency. Tumors that receive a single injection of localized liberase have significantly lower tumor volumes and lower tissue moduli at both the center and edge compared to buffer- and free liberase-injected control tumors, while tissue viscoelasticity remains relatively unaffected. Tumors injected multiple times with LQG and liberase also have lower tissue volumes but possess higher tissue moduli and lower viscoelasticities compared to the other treatment groups. We propose that a mechanotransductive mechanism could cause the formation of smaller but stiffer tumors after repeated, localized liberase injections. Large amplitude oscillatory shear (LAOS) experiments are also performed on tissues from the multiple injection study and the results are analyzed using MITlaos. LAOS analysis reveals that all 4T1 tumors from the multiple injection study exhibit nonlinear rheological behavior at high strains and strain rates. Examination of the Lissajous-Bowditch curves, Chebyshev coefficient ratios, elastic moduli, and dynamic viscosities demonstrate that the onset and type of nonlinear behavior is independent of treatment type and elastic modulus, suggesting that multiple liberase injections do not affect the nonlinear viscoelasticity of 4T1 tumors.

Duke Scholars

Published In

Biomater Sci

DOI

EISSN

2047-4849

Publication Date

March 14, 2023

Volume

11

Issue

6

Start / End Page

2186 / 2199

Location

England

Related Subject Headings

  • Thermolysin
  • Rheology
  • Neoplasms
  • Mice
  • Mechanotransduction, Cellular
  • Collagenases
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 1004 Medical Biotechnology
 

Citation

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ICMJE
MLA
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Corder, R. D., Vachieri, R. B., Martin, M. E., Taylor, D. K., Fleming, J. M., & Khan, S. A. (2023). Linear and nonlinear rheology of liberase-treated breast cancer tumors. Biomater Sci, 11(6), 2186–2199. https://doi.org/10.1039/d3bm00038a
Corder, Ria D., Robert B. Vachieri, Megan E. Martin, Darlene K. Taylor, Jodie M. Fleming, and Saad A. Khan. “Linear and nonlinear rheology of liberase-treated breast cancer tumors.Biomater Sci 11, no. 6 (March 14, 2023): 2186–99. https://doi.org/10.1039/d3bm00038a.
Corder RD, Vachieri RB, Martin ME, Taylor DK, Fleming JM, Khan SA. Linear and nonlinear rheology of liberase-treated breast cancer tumors. Biomater Sci. 2023 Mar 14;11(6):2186–99.
Corder, Ria D., et al. “Linear and nonlinear rheology of liberase-treated breast cancer tumors.Biomater Sci, vol. 11, no. 6, Mar. 2023, pp. 2186–99. Pubmed, doi:10.1039/d3bm00038a.
Corder RD, Vachieri RB, Martin ME, Taylor DK, Fleming JM, Khan SA. Linear and nonlinear rheology of liberase-treated breast cancer tumors. Biomater Sci. 2023 Mar 14;11(6):2186–2199.
Journal cover image

Published In

Biomater Sci

DOI

EISSN

2047-4849

Publication Date

March 14, 2023

Volume

11

Issue

6

Start / End Page

2186 / 2199

Location

England

Related Subject Headings

  • Thermolysin
  • Rheology
  • Neoplasms
  • Mice
  • Mechanotransduction, Cellular
  • Collagenases
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 1004 Medical Biotechnology