Scale invariance of mechanical properties in the developing mammalian retina

The computational capabilities of the human central nervous system arise from neuronal architectures. Neuronal tissues are built through force-driven physical remodeling over durations ranging from seconds to days. However, how cell-generated forces accumulate and relax to drive neurogenesis remains unknown due to the difficulty of applying stresses (i) in developing mammalian nervous tissue, (ii) directly within the cellular microenvironment, and (iii) for durations spanning seconds to hours. Previous studies have shown that non-neuronal tissues and cells in 2D culture remodel in scale-free manners. Whether and how this translates to developing neuronal tissues remains an open question. Here, we probed the mechanics of mammalian neuronal tissue on developmental timescales. We accessed developing mammalian neuronal tissue using retinal organoids, stem-cell-derived models of the retina. To probe mechanics at scales relevant for retinal development, we used magnetic droplets as long-term mechanical actuators. We recorded strain responses to applied stresses across four orders of magnitude in time, up to one hour. We found that dynamic creep compliance and tensile moduli follow a power law with an exponent consistent with a material just above the glass transition. This scale-free rheology represents an unprecedented description of nervous tissue mechanics on developmental timescales and opens the door to a biophysical understanding of the emergence of functional neuronal architectures.