(340d) Intracellular Mass Transport Estimation Using Quantitative Phase Microscopy

Metastasis is the cause of 90% of cancer deaths. Cancer cells metastasis is a result of dysregulation of both mechanical properties and growth. Therefore there is a need for approaches which are capable of quantifying both cell mechanical properties as well as their growth in order to study cancer metastasis and to develop and deploy effective therapies. In this work we apply concepts and approaches from fluid mechanics to study cell mechanics based on quantitative phase imaging of living cells, a platform that has demonstrated utility in measurement of cancer cell growth.¹

Quantitative phase microscopy (QPM) is a label-free, non-invasive imaging method which quantifies the total mass and mass distribution of single living cells. The principle of QPM is as follows: the combination of cell refractive index and thickness slows down light passing through a cell, resulting in a shift in phase relative to light passing through the surrounding media. This phase shift measurement can be used to compute cell mass using the known specific refractive index increment for cell biomass.^1,2 In biomedical applications, QPM data can be used to track total cell biomass over time to measure cell growth³ or the decrease in growth rate caused by treatment of a cancer cell with an effective therapeutic.^4,5 QPM data also reveal the dynamics of cell mass motion, which is linked to cell mechanical properties.⁶

The focus of this work is the estimation of mass transport rate using QPM data. The cell is considered to be a viscoelastic fluid which obeys non-Newtonian behavior. The velocity of mass transport can then be estimated using particle tracking approaches common in experimental fluid mechanics. In this talk we will present our approach as well as the utility of this method to monitor mass redistribution and generation inside cancer cells as a measure of cancer cell growth and disease progression.

References

1. Zangle TA, Teitell MA. Live-cell mass profiling: an emerging approach in quantitative biophysics. Nat. Methods. 2014;11(12):1221-1228.

2. Barer R. Interference microscopy and mass determination. Nature. 1952;169:366-367.

3. Mir M, Wang Z, Shen Z, et al. Optical measurement of cycle-dependent cell growth. Proc. Natl. Acad. Sci. USA. July 25, 2011 2011;108(32):13124-13129.

4. Reed J, Chun J, Zangle TA, et al. Rapid, massively parallel single-cell drug response measurements via live cell interferometry. Biophys. J. 2011;101(5):1025-1031.

5. Chun J, Zangle TA, Kolarova T, Finn RS, Teitell MA, Reed J. Rapidly quantifying drug sensitivity of dispersed and clumped breast cancer cells by mass profiling. Analyst. 2012;137:5495-5498.

6. Eldridge WJ, Steelman ZA, Loomis B, Wax A. Optical Phase Measurements of Disorder Strength Link Microstructure to Cell Stiffness. Biophys. J. Feb 28 2017;112(4):692-702.