Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Poster Abstracts

13-POS Board 13 THE INFLUENCE OF NEIGHBORING CELLS ON CELL STIFFNESS IN A BREAST CANCER MODEL AND MYELOMA Martin Guthold 1 ; Xinyi Guo 1 ; Keith Bonin 1 ; Wu Dan 2 ; Xiaobo Zhou 2 ; Background. Over the last several years, numerous studies have shown that cancer cells and normal cells have different physical properties. Cells interact with each other and with their substrates, and questions how the micro-environment affects physical properties of cells remain unanswered. Methods and Objective. Using an Atomic Force Microscope (AFM) with a 5.3 mm diameter spherical probe, we investigated how neighboring cells affect cell mechanical properties in a breast cancer model and in myeloma. Results. We found that neighboring cells have a significant, complex effect on cell mechanical properties in both systems. Human Mammary Epithelial Cells and cancer derivatives. We obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic and metastatic phase. We also found a distinct contrast in the influence of a cell’s microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than isolated cells. This stiffening effect was not seen in the cancer cell lines, indicating that the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Myeloma. We studied the effect of myeloma cells on bone marrow stromal cells (BMSCs). We found that the higher stiffness of BMSCs was not a unique characteristic of BMSCs from multiple myeloma (MM) patients (M-BMSCs). BMSCs from MGUS (Monoclonal gammopathy of undetermined significance) patients were also stiffer than the BMSCs from healthy volunteers (N-BMSCs). The stiffness of M-BMSCs was enhanced when co-cultured with myeloma cells. In contrast, no changes were seen in myeloma cell-primed MGUS- and N-BMSCs. Our findings demonstrate that CD138- myeloma cell-directed cross-talk with BMSCs and reveal that CD138- myeloma cells regulate M-BMSC stiffness through SDF-1/CXCR4/AKT signaling. 1 Wake Forest University, Physics, Winston-Salem, NC, USA 2 Wake Forest University, Radiology, Winston-Salem, NC, USA

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