Studying the “Phagocytic” behavior of cancer cells in different mechanical conditions

Organs and tissues differ physically from one another in terms of their mechanical properties. Cells are affected by different mechanical microenvironment stiffnesses, causing them to respond in several ways. When cells adhere to surfaces of varying rigidities, changes in their morphology occur, in addition to alteration in their motility, proliferation and differentiation state. Mechanical properties of cells control not only their ability to migrate and colonize in different environments but also their ability to deform, engulf and uptake sub-micron and micro-particles. Since particles are utilized as vehicles for drug delivery, their interaction with cells is crucial for proper distribution and for the efficacy of drugs.

Our objective was to study how the surface rigidity affects the behavior of cancer cells, and particularly, the uptake of sub-micron particles by cells.

In this work we performed detailed uptake experiments in human pancreatic and breast adenocarcinoma cancer cells plated on gels of varying rigidity. Fabricated polyacrylamide hydrogels as well as commercial silicone gels, exhibiting a physiologically relevant range of Young`s modulus, were utilized as a stiffness-controlled platform. The experiments were performed with 0.8 and 2.4 µm fluorescently labelled beads that were incubated with the cells for varying durations. Using imaging flow cytometry, that allows cell image and particle localization analysis, we quantified the efficiency of particle uptake into the cells.

We conclude that the mechanical properties of tissues can have a significant influence on the biodistribution of DDS. These results lay the basis for developing a method to predict the biodistribution and targeting of drug vehicles to different organs and to tumors at varied stages, based on their mechanical properties. These findings may further be developed as a tool for selective delivery to certain organs in the body, and specifically to tumor tissues. Moreover, based on the stiffness-dependent cell interactions with particles, additional physical parameters may be identified and used to improve targeted drug delivery systems and their selective uptake, substantially reducing the off-target exposure of drugs.