Abstract
Uptake of particles by cells involves various natural mechanisms that are essential for their biological functions. The same mechanisms are used in the engulfment of synthetic colloidal drug carriers, while the extent of the uptake affects the biological performance and selectivity. Thus far, little is known regarding the effect of external biomechanical stimuli on the capacity of the cells to uptake nano and micro carriers. This is relevant for anchorage-dependent cells that have detached from surfaces or for cells that travel in the body such as tumor cells, immune cells and various circulating stem cells. In this study, we hypothesize that cellular deformability is a crucial physical effector for the successful execution of the phagocytosis-like uptake in cancer cells. To test this assumption, we develop a well-controlled tunable method to compare the uptake of inert particles by cancer cells in adherent and non-adherent conditions. We introduce a self-designed 3D-printed apparatus, which enables constant stirring while facilitating a floating environment for cell incubation. We reveal a mechanically mediated phagocytosis-like behavior in various cancer cells, that was dramatically enhance in the detached cell state. Our findings emphasize the importance of including proper biomechanical cues to reliably mimic certain physiological scenarios. Beyond that, we offer a cost-effective accessible research tool to study mixed cultures for both adherent and non-adherent cells.
Highlights
In order to perform controlled particle uptake studies in floating conditions compared to traditional adherence measurements, we designed the 3D-printed a continuous flow system (3DCFS) as a device compatible to a standard laboratory stirrer that was utilized to generate motion in a rotor
Cancer cells of solid tumors are an example of cells that normally adhere to ECM, but the epithelial to mesenchymal transition (EMT)
Our observations revealed the major role of cell biomechanics derived from cells’
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Interactions of cells with particles are essential for various biological processes, including pathogens neutralization, the elimination of cell debris and molecular signaling [1,2,3]. Synthetic particulate systems in the form of nano and micro carriers are widely used in drug delivery and targeted therapy. Measuring interactions of particle formulations with cells and tissues is essential for the performance assessment of drug vehicles, and for their optimization. Since carriers can contain active compounds, the issue of their uptake by cells is critical for the safety and efficacy of the treatment [4,5,6,7] and for drug targeting [8]
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