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Communication Dans Un Congrès Année : 2014

PDMS MICRODEVICE ARRAYS FOR MEASURING THE FORCES EXERTED BY GROWING MULTICELLULAR TUMOR SPHEROIDS

Résumé

This paper presents a novel technique for measuring the mechanical forces exerted by a living MultiCellular Tumor Spehroid (MCTS) during growth. We used high aspect ratio microfabricated polydimethylsiloxane (PDMS) pillars as force sensors. During growth, spheroids induce a deformation of the micropillars, which is the parameter we used in order to measure the exerted forces. From 3 dimensional imaging of micropillars induced deflection and mechanical simulation, we were able to measure the force exerted by mammary cancer cell (MCF7) spheroids. Using this methodology we found a value of force of the order of 100-300 nanoNewtons. INTRODUCTION Tumor cells are known to be sensitive to external mechanical stimuli but little is known about the intrinsic growth-associated mechanical properties of micro-tumors [1]. In that context, the changing forces that a micro-tumor exerts on its microenvironment need to be better characterized. A MCTS is a 3D complex system that reproduces cell-cell and cell-matrix interactions and exhibits a cellular architecture that mimics micro-tumor organization. Many approaches have been developed to study the mechanical properties of spheroids. It includes cellular capsules to measure the pressure exerted by a spheroid [2], parallel plate tensiometry for rheological studies [3] or the micropipette technique to study the response of cellular aggregates to external stresses [4]. Our work differs from those mentioned before, firstly, by its high throughput and the ability to investigate a large number of spheroids within the array of microdevices at the same time. Secondly, our system enables to measure the force directly exerted by the spheroid during growth on its surrounding in the nanoNewton scale and for a large period of time without a drastic perturbation of the cell organization within the spheroid under investigation. EXPERIMENTAL The produced devices are arrays of high aspect ratio (1:10), round and flexible PDMS pillars, of 300 µm in height, identical in diameter and circularly distributed around a space where the spheroid will be placed. Each pillar is used as a force sensor by a simple recording of its bending. We fabricated devices of different pillar diameters in order to study the effect of the stiffness on the intensity of the generated forces. The technological challenge behind these devices was the optimization of a process capable to produce PDMS beams high enough compared to the MCTs (around 300 µm), soft enough (stiffness around 10 nN/µm) for measuring nano-newton scale forces, while preventing their mechanical collapse [5]. In order to measure forces exerted by growing spheroids, the deformations of the pillars and the contact zone of the spheroid with the microdevice are required. The growth of cancer cells spheroids was recorded by taking 3D confocal images for fluorescently stained microdevices and cells expressing a fluorescent marker (Figure 1).
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Dates et versions

hal-01097774 , version 1 (22-12-2014)

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  • HAL Id : hal-01097774 , version 1

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Laurene Aoun, Stanislas Larnier, Pierre Weiss, Ariane Herbulot, Bernard Ducommun, et al.. PDMS MICRODEVICE ARRAYS FOR MEASURING THE FORCES EXERTED BY GROWING MULTICELLULAR TUMOR SPHEROIDS. The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014), Oct 2014, San Antonio, Texas, United States. ⟨hal-01097774⟩
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