Transition Between Collective Mechanical Instabilities in 3D Printed Microtissues

Collective cell migration and multicellular forces in monolayers have been studied extensively, but collective behaviors in 3D systems are relatively unexplored due to the challenges of creating well defined 3D structures. Simple 3D systems for studying collective cell behavior include spheroids and cells dispersed in extracellular matrix. Spherical aggregates act like fluid drops, exhibiting an effective surface tension created by cell-cell cohesion. Cells embedded in ECM contract their surroundings forming a stressed structure, which likely comes to a balance between cell tension and ECM compression. To systematically study collective mechanical behavior, we 3D print microbeams of collagen and glioblastoma cells at different collagen concentrations. These cell/ECM microbeams are printed directly into a jammed microgels of varying material properties. In microgels with large elastic moduli, the microtissues are immobile. As we lower the modulus of the microgel, the microtissues become unstable and break into drop-like shapes. When the modulus is lowered further, the microbeams undulate with a wavelength predicted by Euler-Bernoulli beam theory. Measurements of these phenomena allow us to predict stress of cells as a function of material properties of their microenvironment.