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An Automated High-throughput Array Microscope for Cancer Cell Mechanics.

Jeremy A Cribb¹, Lukas D Osborne¹, Kellie Beicker¹

¹Department of Physics and Astronomy, UNC-Chapel Hill, Chapel Hill, NC, United States of America.

Scientific Reports

|June 7, 2016

Summary

This study introduces a new high-throughput microscope system to measure cell mechanical properties, crucial for understanding cancer metastasis and drug screening. The system successfully identified changes in cell compliance related to the epithelial-to-mesenchymal transition (EMT).

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Area of Science:

Biophysics
Cell Biology
Cancer Research

Background:

Cellular mechanical properties change during epithelial-to-mesenchymal transition (EMT), a process linked to cancer metastasis.
Existing high-throughput methods for measuring cell compliance are limited, hindering research into genetic alterations and drug efficacy screening.

Purpose of the Study:

To develop and validate a novel array high-throughput microscope (AHTM) system for measuring cell mechanical properties.
To assess the AHTM's capability in screening for changes in cell compliance related to EMT.

Main Methods:

Development of an AHTM system combining 96-well plate format with simultaneous imaging of cells and microbeads across twelve channels.
Application of passive bead rheology techniques using the AHTM to measure the relative compliance of various human pancreatic ductal epithelial cell types and EMT-related constructs.

Main Results:

The AHTM system was successfully developed and demonstrated its ability to image cells and microbeads efficiently.
Increased cell compliance was observed in h-TERT transformed HPDE cells (HPNE) and cells transfected with H-ras, Myr-AKT, and Bcl2 constructs.
Results from the AHTM correlated with atomic force microscopy and invasion assays, validating its accuracy in detecting mechanical phenotype changes.

Conclusions:

The developed AHTM system is a viable high-throughput tool for measuring cell mechanical properties.
The AHTM can effectively screen for changes in cell compliance associated with EMT and potentially other cellular processes.