Cellular traction forces (CTFs) play a role in many physiological and disease processes, including cell migration, cancer metastasis, stem cell differentiation, wound healing, and synapse formation. Traction force microscopy (TFM) is a family of optical techniques used to quantify CTF. Typical methods for 3D TFM are based on confocal fluorescence microscopy, and can suffer from limited penetration depth, slow acquisition speeds, and photobleaching/phototoxicity concerns. Our lab developed traction force optical coherence microscopy (TF-OCM) to overcome these challenges and enable 4D TFM for the study of both single cells and multi-cellular constructs in scattering media. We collaborate with the Fischbach Lab to apply our new imaging capabilities to study biomechanical cell-matrix interactions in physiologically-relevant tumor spheroid systems.
Computational 4D-OCM of collective cell invasion into surrounding collagen matrix by adipose stromal cell spheroid. Top row: depth projection of traditional OCM image (left), temporal speckle contrast delineating green ‘cell’ and gray-scale ‘collagen’ channels (middle), and depth-to-color projection of cell channel. Bottom row: 3D rendering and 3D rendering with cutaway of cell channel.
- Mulligan J.A., Ling L., Leartprapun N., Fischbach C., Adie S.G., “Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen”, Scientific Reports, 11, Article number: 2814, 2021.
- Ling L., Mulligan J.A., Ouyang Y., Shimpi A.A., Williams R.M., Adie S.G., Fischbach C., “Obesity-associated adipose stromal cells promote breast cancer invasion through direct cell contact and ECM remodeling”, Advanced Functional Materials, 1910650 (1-13), 2020.
- Mulligan, J.A., Feng, X. & Adie, S.G. “Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy,” Sci. Rep., 9, 4086, 2019.
- Mulligan J.A., Bordeleau F., Reinhart-King C.A. and S.G. Adie, “Traction Force Microscopy for Non-Invasive Imaging of Cell Forces”, In Biomechanics in Oncology, Editors: Dong C., Kuhn N., and Konstantopoulos K., Springer, Vol. 1092, 2018.
- Mulligan, J.A., Bordeleau, F., Reinhart-King, C.A., Adie, S.G. “Measurement of dynamic cell-induced 3D displacement fields in vitro for traction force optical coherence microscopy,” Biomed. Opt. Express, 8, 1152-1171, 2017.