Actuoids: guided tissue morphogenesis using soft actuation

Lab-grown mini-organs known as organoids are far from the real thing — while these tiny clumps of tissue derived from human stem cells are yielding more insights about human biology than individual cells grown in a dish, they’re missing several key elements of actual organs. One important missing factor may come from a lack of physical structure and pressure on the clumps as they develop; our own organs are subject to many mechanical forces during development that influence their shape and identity. Adrian Ranga, Ph.D., is leading a project to apply the emerging field of “soft robotics” to brain organoid development, using newly developed materials and devices to stretch and fold brain organoids as they grow. Their hope is to generate brain organoids that more closely mimic a real portion of the developing human brain; specifically, ones that fold into a central neural tube and that develop distinct layers of tissue. More realistic brain organoids have the potential to improve drug discovery for human brain diseases and disorders as well as influence the field of regenerative medicine. 

Affiliated Investigators

Adrian Ranga, Ph.D.

KU Leuven

Adrian Ranga is an Assistant Professor in the Department of Mechanical Engineering at KU Leuven. His research explores principles of development using engineered biomimetic model systems. Dr. Ranga obtained his Ph.D. in life sciences from EPFL, where he established combinatorial synthetic hydrogel microarrays to study the role of the microenvironment in neural tube organoids in the laboratory of Matthias Lutolf. He then received an SNF post-doctoral fellowship to join the laboratory of Olivier Pourquié at Harvard Medical School, where he initiated somitoids, an in-vitro model of paraxial mesoderm patterning. 

Since starting his lab at KU Leuven, Dr. Ranga’s main research focus has been to understand how mechanical forces coordinate neural patterning, morphogenesis and growth by designing enabling technologies to guide in-vitro synthetic development. His group develops context-specific artificial extracellular matrices, soft 3D microfluidics, mechanical actuation devices, and functional biosensors to generate mechanically dynamic cellular microenvironments. He has introduced the concept of actuoids, where in-vitro multicellular systems are actuated using customized mechanical devices. His lab has shown that recapitulating the active mechanical forces seen during in-vivo development enhances patterning of neural tube organoids, and that this response is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility. His group is now unraveling the molecular mechanisms underlying these phenomena using spatial transcriptomic and agent-based modeling approaches. Dr. Ranga’s lab also develops modular microfluidic devices to microvascularize organoids and create programmable morphogen fields to shape synthetic morphogenesis. The combination of these technologies provides a bottom-up approach to study the emergence of mammalian neural organization and function during development.