Optical Cellular Micromotion: A New Paradigm to Measure Tumor Cells Invasion within Gels Mimicking the 3D Tumor Environments

Zhaobin Guo, Chih Tsung Yang, Chia Chi Chien, Luke A. Selth, Pierre O. Bagnaninchi, Benjamin Thierry

Research output: Contribution to journalArticlepeer-review

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Abstract

Measuring tumor cell invasiveness through 3D tissues, particularly at the single-cell level, can provide important mechanistic understanding and assist in identifying therapeutic targets of tumor invasion. However, current experimental approaches, including standard in vitro invasion assays, have limited physiological relevance and offer insufficient insight into the vast heterogeneity in tumor cell migration through tissues. To address these issues, here the concept of optical cellular micromotion is reported on, where digital holographic microscopy is used to map the optical nano- to submicrometer thickness fluctuations within single-cells. These fluctuations are driven by the dynamic movement of subcellular structures including the cytoskeleton and inherently associated with the biological processes involved in cell invasion within tissues. It is experimentally demonstrated that the optical cellular micromotion correlates with tumor cells motility and invasiveness both at the population and single-cell levels. In addition, the optical cellular micromotion significantly reduced upon treatment with migrastatic drugs that inhibit tumor cell invasion. These results demonstrate that micromotion measurements can rapidly and non-invasively determine the invasive behavior of single tumor cells within tissues, yielding a new and powerful tool to assess the efficacy of approaches targeting tumor cell invasiveness.

Original languageEnglish
Article number2200471
Number of pages13
JournalSmall Methods
Volume6
Issue number8
Early online date28 Jun 2022
DOIs
Publication statusPublished - 18 Aug 2022

Keywords

  • 3D cell environments
  • cellular migration
  • digital holographic microscopy
  • micromotion
  • nanoscale optical thickness fluctuations

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