Emergent collective organization of bone cells in complex curvature fields

Abstract

Individual cells and multicellular systems have been shown to respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra, partly owing to fabrication limitations and the lack of formal geometric considerations. Here, we show that micro-engineered substrates with controlled curvature variations induce the collective spatiotemporal organization of preosteoblasts. By leveraging mathematical surface design and a high-resolution free-form fabrication process, we exposed cells to a broad yet controlled, heterogeneous spectrum of curvature fields. We quantified curvature-induced spatial patterning at different time points and found that cells generally prefer regions with at least one negative principal curvature. We also show that multicellular cooperation enables cells to venture into unfavourably-curved territories, bridging large portions of the substrates, and collectively aligning their stress fibres. We demonstrate that this behaviour is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer unifying perspectives on cell-geometry interactions that could be harnessed in the design of micro-engineered biomaterials, for example, for tissue engineering applications.

Soft pneumatic actuators for mimicking multi-axial femoropopliteal artery mechanobiology

“…We observed that devices with microgrooved surfaces had improved cellular attachment over devices with smoothed surfaces, thus we used microgrooved devices for all SPA conditioning studies. While previous studies have shown that similar microscale topologies can affect cellular morphology and alignment [41,42], we observed no significant cell alignment in static culture (SC) replicates due to the microgrooves (figures S2(B) and (C)). Future investigations into how cells respond to competing mechanobiological stimuli would aid in decision-making when choosing the most effective methods for guiding tissue maturation.…”

Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales

“…[156] On 3D sinusoid landscapes, individual cells position themselves in concave regions [4b] but collections of cells coordinate to reach favorable tensional states that allow them to colonize other regions. [157] In concavities, the oriented tension accumulated in the multicellular system often results in tissue detachment. [158] Similarly, epithelial cells grown on flat fibronectincoated substrates with circular nonadhesive islands of various sizes were also observed to spontaneously depart from the surface and form domes of different radii of curvature.…”

Bio-hybrid Soft Robotic Bioreactors for Mimicking Multi-Axial Femoropopliteal Artery Mechanobiology

“…The additively manufactured BSR molds resulted in microscale 3D printing layer lines across the BSR and its recesses and imaged ROIs. Previous studies have shown that similar microscale topological features can affect cellular morphology and alignment [46, 47]. However, no significant cell alignment due to these layer lines was observed for static culture (SC) replicates.…”