Effect of Substrate Rigidity
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Effect of Substrate Rigidity On Breast Cancer Cells Elizabeth L. Smith, RET Fellow 2011 West Aurora High School RET Mentor: Dr. Michael Cho, PhD NSF- RET Program. Abstract. Motivation.

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PDMS is not a hospitable surface for cell adhesion

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Pdms is not a hospitable surface for cell adhesion

Effect of Substrate RigidityOn Breast Cancer Cells Elizabeth L. Smith, RET Fellow 2011West Aurora High SchoolRET Mentor: Dr. Michael Cho, PhDNSF- RET Program

Abstract

Motivation

Cancer cells interact with the environment around them in a bidirectional manner. While metastatic cells modify the environment and navigate through it, the environment exerts significant influence over the cell’s shape, structure, and behavior.2,3,4,5

This study was designed to examine how two breast cancer lines, MB231 and MCF7, respond to PDMS (polydimethylsiloxane) substrates that differ in the rigidity by an order of magnitude.

Less invasive MCF7 cells adhere poorly to PDMS independent of the rigidity, suggesting lack of focal adhesion. Highly invasive MB231 cells showed greater proliferation on the soft substrate, as well as significantly greater actin fibers and focal adhesions. Invasive MB231 cells alter their structure based on substrate rigidity.

Understanding the rigidity-dependent cancer cell behavior may lead to development of better cancer diagnoses, therapies, and potentially cures.

1 in 8 women in the U.S. will be diagnosed

with breast cancer in their lifetime

Breast cancer is the

second deadliest cancer in women1

Hypothesis

Hypothesis

Breast cancer cells will change structure

in response to varying substrate stiffness

Material and Methods

100 um

MB231 cell growing on 10:1 PDMS at 40x magnification

Results

Cells Structure Analysis

MB231 Cell Line

Average Number of Cells per View

MB231 Cell Line

Invasive MB231 Cells on

Rigid Substrate

- Lower cell density

- Greater actin fibers

- Greater focal adhesions

Invasive MB231 Cells on

Soft Substrate

- Higher cell density

- Lesser actin fibers

- Lesser focal adhesions

Day 1

Day 7

Rigid Substrate

10:1 PDMS

Conclusion

Acknowledgements

*

Statistical

Significance

Soft Substrate

30:1 PDMS

  • NSF Grant CBET-EEC-0743068

  • Prof. A. Linninger, RET Program Director

  • Dr. Michael Cho, Research Advisor

  • Brandon Lutz, Research Mentor

  • University of Illinois- Chicago

  • PDMS is not a hospitable surface for cell adhesion

  • Lack of adhesion shows MCF7 cells retain characteristics of noncancerous cells

  • PDMS is not a hospitable surface for cell adhesion

  • Adhesion of cells shows that MB231 cells have unique adaptive abilities not found in noncancerous cells

References

1. Breastcancer.org (April 19th, 2011). U.S. Breast CancerStatistics. Breastcancer.org.Retrieved July 26, 2011, from http://www.breastcancer.org/symptoms/understand_bc/statistics.jsp

2. Curtis, A., & Wilkinson, C. (January 01, 1997). Topographical control of cells. Biomaterials, 18, 24, 1573.

3. Guo, W. H., Frey, M. T., Burnham, N. A., & Wang, Y. L. (January 01, 2006). Substrate rigidity regulates the formation and maintenance of tissues. Biophysical Journal,90, 6, 2213-20.

4. Rapier, R., Huq, J., Vishnubhotla, R., Bulic, M., Perrault, C. M., Metlushko, V., Cho, M., ... Glover, S. C. (January 01, 2010). The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells. Cancer Cell International, 10.

5. Tzvetkova-Chevolleau, T., Stéphanou, A., Fuard, D., Ohayon, J., Schiavone, P., & Tracqui, P. (January 01, 2008). The motility of normal and cancer cells in response to the combined influence of the substrate rigidity and anisotropic microstructure. Biomaterials,29, 10, 1541-51.

  • MB231

  • Invasive Breast Cancer

  • MCF7

  • Less invasive Breast Cancer

Future studies may include further analysis of:

- Cell mobility- Surface proteins- Size & shape of focal adhesions

- Cell rigidity- Intercellular signaling and actin fibers


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