Abstract
Growing multicellular spheroids recapitulate many features of expanding microtumours, and therefore they are an attractive system for biomechanical studies. Here, we report an original approach to measure and characterize the forces exerted by proliferating multicellular spheroids. As force sensors, we used high aspect ratio PDMS pillars arranged as a ring that supports a growing breast tumour cell spheroid. After optical imaging and determination of the force application zones, we combined 3D reconstruction of the shape of each deformed PDMS pillar with the finite element method to extract the forces responsible for the experimental observation. We found that the force exerted by growing spheroids ranges between 100nN and 300nN. Moreover, the exerted force was dependent on the pillar stiffness and increased over time with spheroid growth.
Highlights
Sensing compression and tension forces is an important component of cell physiology
Inspired by the strategy of arrays of discrete microfabricated pillars of silicone elastomer to measure forces exerted by single cells [12, 13], we previously developed a technological process for fabricating high aspect ratio polydimethylsiloxane (PDMS) micropillars (300μm in height) with different diameters adapted to the characterization of the mechanical interactions between a growing multicellular tumour spheroid and its environment
We previously developed biocompatible ring-shaped microdevices composed of arrays of high aspect-ratio flexible PDMS pillars that can be used as force microsensors to investigate the mechanical forces of multicellular tumour spheroids[14]
Summary
Sensing compression and tension forces (i.e., mechanosensing) is an important component of cell physiology. Solid tumour growth is associated with stiffening of the tumour tissue due to cell proliferation and modification of the extracellular matrix components Such tissue stiffening involves the generation of mechanical forces that accumulate within the growing tumour and that, in turn, are applied on and deform the surrounding tissue [1, 2]. Jain and collaborators demonstrated that these mechanical forces induce vessel compression and increase the interstitial fluid pressure, affecting drug delivery [10].
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