(62d) Effect of Tumor Secreted Soluble Factors On Mesenchymal Stem Cell Microrheology and Heterogeneity of the Cytoskeletal Network

Mesenchymal Stem Cells (MSCs) are a multipotent adult bone marrow (BM) derived stem cell that spontaneously migrate from the BM in response to tumor secreted soluble factors to integrate in tumors [1]. Though actin polymerization is a key step in cell mobility [2], it is unclear how this cytoskeletal reorganization affects the microrheological properties. Previous studies have shown that increased concentrations of actin, leading to increased polymerization, creates more heterogeneity in solution [3]. Using multiple particle tracking, the Brownian motion of 100nm fluorescent particles is tracked to derive the ensemble-averaged mean squared displacement (MSD), which after undergoing a Fourier transformation is used to calculate frequency-dependent complex viscoelastic modulus (G*) and then separated into the elastic (G`) and viscous (G``) moduli [4]. Despite the ex vivo studies, in vitro the heterogeneity of particles noticeably decreases. Furthermore, after treatment the cells transition from primarily viscous to primarily elastic rheology, suggesting the reorganization of globular actin to f-actin is modulated by these tumor secreted molecules. Chapel, A., et al., Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J Gene Med, 2003. 5(12): p. 1028-38. 2. Uribe, R. and D. Jay, A review of actin binding proteins: new perspectives. Molecular Biology Reports, 2009. 36(1): p. 121-125. 3. Apgar, J., et al., Multiple-particle tracking measurements of heterogeneities in solutions of actin filaments and actin bundles. Biophysical Journal, 2000. 79(2): p. 1095-1106. 4. Mason, T.G. and D.A. Weitz, OPTICAL MEASUREMENTS OF FREQUENCY-DEPENDENT LINEAR VISCOELASTIC MODULI OF COMPLEX FLUIDS. Physical Review Letters, 1995. 74(7): p. 1250-1253.