Poster

Magnetically controlled micro-deformation of 3D tumor models for mechanobiological in situ studies

Daphne O. Asgeirsson¹, Avni Mehta¹, Nicolas Hesse¹, Michael G. Christiansen¹, Anna Scheeder², Andrea De Micheli³, Simone Schuerle-Finke¹

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Changes in the mechanical properties of tissues are known to both indicate and drive the progression of pathological conditions such as tumor growth and malignancy.[1,2] Consequently, large interest has grown in the development of methods to characterize and control the mechanics of tissues in vivo and in vitro. As such, the stiffness and perfusion of cell environments is increasingly considered, and (cyclic) stretch and compression of samples have been implemented at different scales, ranging from nanoscale structures to bulk samples.[3]
Macroscale approaches report bulk continuum properties of investigated materials but fail to resolve the local stiffness heterogeneity inherent to extracellular fiber networks and the embedded cells.[4] As active building blocks of tissues, individual cells sense and react to mechanical cues in their microenvironment. Further, they deform and remodel their surrounding structures at the nano- to microscale by exerting forces in the range of a few to tens of pNm.[5,6]

To take on the perspective of individual cells residing within 3D in vitro tissue models, we used rod-shaped magnetic microparticles (μRods) to probe and manipulate sample volumes at a microscale. Based on the principle of magnetic rotation spectroscopy, an eight-coil electromagnetic field generator combined with high-resolution optical microscopy enabled us to analyze the deflection of hydrogel-embedded μRods in response to rotating magnetic fields and determine locally apparent shear values within fibrous 3D Collagen I (Col I) hydrogels. Complementary analysis of fluorescently labelled Col I networks indicated that magnetically controlled deflection of embedded μRods resulted in network deformation that propagated across a distance spanning multiple times the length of a single μRod.[7] Next, we investigated effects of long-term micromechanical actuation of μRod-enriched 3D tissue models under standard cell culture conditions. A motor-driven Halbach-cylinder was used to provide a uniform rotating magnetic field. Using MDA-MB-231 spheroids embedded in Col I hydrogels as example, we investigated to which extent cancer cell invasion is affected by sustained cyclic micro-deformation of the microenvironment over several days of culture.

The proposed methodology aims to complement current approaches for probing mechanosensitive cues in biomimetic in vitro models. Eventually, insights gained from such investigations could then accelerate the development of drugs that target mechanical signaling pathways.