Mareike Zink¹, Franziska Wetzel¹, Anatol Fritsch¹, Steve Pawlizak¹, Tobias Kießling¹, K. David Nnetu¹, Lars-Christian Horn², Michael Höckel³, Josef A. Käs¹
 

1		Soft Matter Physics Division, Institute of Experimental Physics I, University of Leipzig, Linnéstraße 5, 04103 Leipzig, Germany
2		Division of Breast, Gynecologic & Perinatal Pathology, Institute of Pathology, University of Leipzig, Liebigstraße 26, 04103 Leipzig, Germany
3		Department of Obstetrics and Gynecology, Medical School, University of Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany
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Biophysics established a new research area which described the progression of cancer from a materials science perspective. It has been know for a long time that malignant transformation is associated with significant changes in the cellular cytoskeleton. If the cytoskeleton’s alterations are necessary for malignant transformation, they have to trigger biomechanical changes that impact cellular functions. In all cancers malignant neoplasia – uncontrolled growth, invasion into the surrounding tissue and metastasis occurs. Our results indicate that all these three phenomechanisms of malignancy require changes in the active and passive biomechanics of a tumor cell. Microfluidic Optical Stretcher (MOS) experiments with tumor cell lines clearly show that malignant transformation causes cell softening for small deformations which correlates with an increased rate of proliferation compared to normal cells. Additionally, three clinical studies were carried out to prove the potential of the MOS for cancer diagnosis. First, primary oral squamous carcinoma cells from patients with early dysplasia and malignant tumors were probed with the MOS and compared with the deformability of primary oral cells from healthy donors. Second, breast tumor cells were resected from the women’s body and deformed within the MOS together with primary normal breast epithelial cells. Third, primary cervical carcinoma cells and normal epithelial cells resected from the same morphological compartment of the same women were examined. From all experiments we clearly found that tumor cells are softer compared to normal cells and exhibit a broader distribution of optical deformability. Since cell softening during malignant transformation seems to be a universal behavior of tumor cells, the MOS offers the possibility to detect many different types of tumors without any further knowledge of the molecular details of the cells. Furthermore, cell softening of the actin cortex can increase individual cell speed for lamellipodial motion of malignantly transformed cells. However, all cells can migrate and the motion of epithelial cells is mainly determined by their environment, whereas fibroblasts have the capability to move freely. Thus, it is the ability of single epithelial cells to overcome the tumor barrier to metastasize. The barrier that cells feel when they try to leave their cell compartment can be lowered by reducing cell-cell adhesion which was studied with CellHesion scanning force microscopy.