Inverse design of three-dimensional multicellular biobots with target functions

Hybrid living biobots consisting of active cells hold promise for significant applications as, for example, intelligent devices in medical engineering and organisms with specific functions in synthetic biology. However, the design and creation of living biobots with various cells remain a challenge. In this paper, we propose a three-dimensional inverse optimization strategy based on the pixel topology optimization method, to design self-propelled living biobots with the function of biomechanical actuations. For illustration, we design several biobots composed of active and passive elements that mimic cardiomyocytes and passive epidermal cells sourced from such as Xenopus Laevis, human induced pluripotent stem cells or neonatal rats. Their topologies are optimized by implementing the active constitutive relations of cells into the multicellular topological interpolation model. Effects of nutrient concentrations, elasticity, and anisotropic contraction of cardiomyocytes on the topologies and functionalities of the biobots are examined. In addition, we unveil the living topological interfaces generated by the collective actuations of the optimized biobots. We show a potential of collective biobots for high-throughput drug screening owing to their distinct biomechanical responses under healthy and sick conditions. The proposed inverse optimization method can be extended to design various functional multicellular biological systems, which impacts the studies of organ development, synthetic biology, and medical engineering.