Multi-photon fluorescence imaging of Doxorubicin

[11]  Carlson M, Watson AL, Anderson L, Largaespada DA, Provenzano PP. Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid tumors. Journal of biomedical optics. 2017 Nov; 22(11):1-9.

non-overlapping model

[9] Klank R.L., Rosenfeld S.S., & Odde D.J. "A Brownian dynamics tumor progression simulator with application to glioblastoma." Convergent Science Physical Oncology, 2018, 4(1):015001.

Dynamics of 3d Carcinoma Cell Invasion

[10] Ray A., Morford R.K., Ghaderi N., Odde D.J., & Provenzano P.P. "Dynamics of 3D carcinoma cell invasion into aligned collagen." Integrative Biology, 2018, In Press.


[8] Estabridis H.E., Jana A., Nain A., & Odde D.J. "Cell migration in 1D and 2D nanofiber microenvironments." Annals of Biomedical Engineering, 2017. In Press.

 Antisotropic Forces
[7] Ray A, Lee O, Win Z, Edward RM, Alford PW, Kim DH, Provenzano PP Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nature Communications 8:14923, 2017

Here we demonstrate how cells to spontaneously ‘sense’ and follow extracellular matrix alignment through anisotropic cell–substratum forces.   Further, this work demonstrates control of contact guidance by a balance of cell–substratum, and cell–cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements.

Shifting Optimal Stiffness for Cell Migration
[6] Bangasser, B.L, G. Shamsan, C.E. Chan, K.N. Opoku, E. Tüzel, B.W. Schlichtmann, J.A. Kasim, B.J. Fuller, B.R. McCullough, S.S. Rosenfeld, and D.J. Odde, “Shifting the optimal stiffness for cell migration,” Nature Communications, 8, Article number: 15313 (2017).

This study demonstrated that the optimal mechanical stiffness of the substrate to which cells adhere, in terms of cell spreading and migration, can be shifted as predicted by the motor-clutch model, i.e. by coordinately changing the motor-clutch level. Thus, the principle difference between neurons and glioma cells is the motor-clutch level, with glioma exhibiting a much higher level of both, and therefore a much higher optimum. The study demonstrates the predictive power of the motor-clutch modeling, and shows how cells establish their optimum.

[5] Provenzano PP, Tug of war at the cell-matrix interface Biophysical Journal, 112(9):1739-1741, 2017

Minireview of mechanotransduction and modeling cell dynamics and the highlight of recent work interfacing the motor-clutch model framework to a mechanically evolving extracellular matrix.

Integrin Mediated Traction Force
[4] Mekhdjian, A.H.*, F.B. Kai*, M.G. Rubashkin*, L.S. Prahl, L.M. Przybyla, A.L. McGregor, E.S. Bell, M.J. Barnes, C.C. DuFort, G. Ou, A.C. Chang, L. Cassereau, S.J. Tan, M.W. Pickup, J.N. Lakins, X. Ye, M.W. Davidson, J. Lammerding, D.J. Odde, A.R. Dunn, V.M. Weaver, “Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix,” Molecular Biology of the Cell,  Apr 5. pii: mbc.E16-09-0654. doi: 10.1091/mbc.E16-09-0654. [Epub ahead of print]. *These authors contributed equally.

This study demonstrated that the epithelial-to-mesenchymal transition (EMT) in breast epithelial cells is largely mediated by a coordinate increase in motors and clutches, with a somewhat larger increase in clutches relative to motors. The findings suggest new ways to inhibit EMT, which is a key step in invasion and metastasis.

[3] Ray A, Slama ZM, Morford RK, Madden SA, Provenzano PP Enhanced Directional Migration of Cancer Stem Cells in 3D Aligned Collagen Matrices, Biophysical Journal, 112(5):1023-1036, 2017

This work demonstrates the unique dynamics of cancer stem cells during directed cell migration by contact guidance in aligned collagenous extracellular matrix.  Further, we show that a high degree of phenotypic plasticity and increased protrusive activity emerge as vital facilitators of rapid contact guided migration of CSCs.

[2] Klank, R.L., Decker Grunke, S.A., Bangasser, B.L., Forster, C.L., Price, M.A., Odde, T.J., SantaCruz, K.S., Rosenfeld, S.S., Canoll, P., Turley, E.A., McCarthy, J.B., Ohlfest, J.R., and D.J. Odde (2017). Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level. Cell Reports, 18, 23-31.

This study demonstrated that there is an optimal level of CD44 that correlates with fastest cell migration in an induced mouse model for glioblastoma. We found that at intermediate CD44 level cells migrated fastest and that mice die most rapidly. If the level of CD44 is either increased or decreased, then migration drops and survival is extended. When we examined published human transcript data, we found the same trend with respect to human high grade glioma survival, even though there was no linear correlation. Thus, our results illustrate the functional relationship between cell migration and survival, and more generally point toward biomarkers being treated as non-monotonic predictors such that survival depends biphasically upon expression level, i.e. there is an optimal level of gene expression leads to poorest outcomes.