The Effect of Stiffness on Cancer Cell Contact Guidance

Koelbl, Joseph
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Chemical and Biological Engineering

Statistics have shown approximately 20% of deaths every year in the US are as a result of cancer. Most of these deaths aren’t caused by the primary tumor, but the migration of cancer cells and their subsequent tumor growth. It has been found that many cells migrate directional using different cues. The directional cues have been identified as electrical gradients, stiffness gradients, chemical gradients, or fiber alignment. Cell migration along aligned fibers is called contact guidance. While these cues have been identified to cause directional migration, there has not been an in-depth study on how cells are responding to these cues.

Our purpose was to characterize the effect of matrix stiffness on contact guidance migration. Collagen fibers were used as the contact guidance platform, since collagen makes up the fibrous region of the extracellular matrix. Mica has been found by our lab to be a good platform to grow aligned collagen fibers due to its ionic surface chemistry and ordered structure. However, mica is stiff and not tunable. In order to characterize cell alignment, a transplantation method was also developed to transfer fibers to polymer surfaces with tunable stiffness like polyacrylamide and polydimethylsiloxane. Alignment and elongation of the cells were characterized through fixing and staining the cells. Long time-lapse migration was examined and speed and persistence of the cells along the fiber cue was calculated. From preliminary results, we could confirm the effectiveness of our transfer method from mica to functionalized polymer surfaces. In addition, stiffer substrates seem to lead to better elongation and alignment with the matrix. This leads us to believe that stiffer extracellular matrices could be worse for cancer cell metastasis.