Particle Uptake Specificity in Cancer: Role of Cell Mechanics

Yifat Brill-Karniely 1 Dvir Dror 1 Yoel Goldstein 1 Ouri Schwob 1 Talya Millo 1 Natalie Orehov 1 Tal Duanis-Assaf 2 Tal Stern 1 Diane Bielenberg 3 Meital Reches 2 Ofra Benny 1
1The Hebrew University of Jerusalem, Israel
2The Hebrew University of Jerusalem, Israel
3Boston Children’s Hospital, USA

Growing evidence shows correlation between cancer aggressiveness and the mechanical properties of tumor cells. Aggressiveness of cancer cells requires mechanical adjustment to varying physical environments during processes like the growth of high pressure tumors, the detachment of metastases forming cells from the tumor, the efficient motion and passage of detaching cells through narrow confinements, and their establishment in a distant tissue. It is not surprising thus that there are clear physical differences between normal and cancer cells as well as between cancer cells of increasing metastatic potential: the more tumorigenic are the cells, the more deformable they are, and of enhanced abilities to adjust to external force.

In our research we aim to use these physical differences for promoting specificity in particle uptake by cells. Such physical based specificity can potentially be used for future rational design of drug delivery systems. For that aim we performed a multidisciplinary research studying how different types of non-cancer and cancer cells, including cells of increasing malignant potential, interact with particles of varying physical properties. A wide range of schemes was used, including FACS, microplate reader, confocal time lapse microscopy, 3D multicellular spheroids, AFM measurements, xenograft in vivo experiments, bioinformatics and physical modelling. Our study provides new mechanistic insights related to cancer progression that can potentially be applied in the rational design of drug delivery systems.

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