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Control of myotube growth for the generation of synthetic muscular micro-actuators

Periodic Reporting for period 1 - MYOFORCE (Control of myotube growth for the generation of synthetic muscular micro-actuators)

Periodo di rendicontazione: 2023-09-01 al 2025-12-31

Living tissues are remarkable materials. They can actively generate forces, adapt their shape, and reorganize themselves in response to internal and external cues. These properties play a central role in how organs form during development and how tissues remodel during health and disease. Yet, despite decades of research, there is still no clear framework to explain how collective cellular forces can be programmed to generate predictable tissue reshaping, which could be used in actuators at the microscale.

The goal of this project was to understand and control how groups of cells generate internal mechanical stresses and how these stresses can be used to drive controlled shape transformations. The project was initially motivated by challenges in biohybrid robotics and soft actuation, where living cells are combined with artificial materials to create active systems. However, a broader motivation was to uncover general physical principles governing tissue morphogenesis for actuation in devices.

The project explored whether cellular orientation and collective organization could be used as a design parameter to control internal stresses and shape changes in living tissues. By combining concepts from physics, biology, and materials science, the project aimed to establish a pathway toward programmable, self-shaping living materials, with potential relevance for bioengineering, morphogenesis research, and the design of adaptive materials.
The project developed experimental platforms in which living cells were cultured on precisely designed surfaces that control how cells align and organize collectively. By tailoring the geometry and directional cues of these surfaces, the project achieved robust control over the orientation of cells across entire tissues.

Mechanical forces generated by the cells were measured using quantitative microscopy techniques, allowing direct mapping of internal stress patterns. While the original plan focused on differentiated muscle tissues, the project identified undifferentiated cell layers as a more reliable and informative system for studying collective mechanics.

A major achievement was the demonstration that specific patterns of cellular alignment create incompatible internal stresses that force flat tissues to deform into three-dimensional shapes. These transformations were reproducible, predictable, and controlled purely by tissue organization, without the need for external mechanical manipulation.

The project also explored optical control strategies, enabling light-based activation of cellular forces and dynamic modulation of tissue mechanics. Together, these approaches led to the discovery of a new mechanism for driving tissue shape changes through internal stress organization.
The project establishes orientation-guided tissue morphing as a new principle for shaping living tissues. Unlike existing approaches based on bending, buckling, or external forcing, this mechanism relies on the frustration of tissue stresses. This represents a conceptual advance in how tissue mechanics and morphogenesis are understood.

The results bridge physics concepts such as orientational order with biological tissue behavior, providing a new framework for studying how complex shapes emerge in living systems. Because similar patterns of cellular alignment are observed in developing and diseased tissues, the findings may also inform future biomedical research.

Beyond biology, the project lays the groundwork for engineering programmable, self-shaping active materials. Instead of designing devices with predefined mechanical parts, shape change can be encoded directly into the internal organization of the material. Further research could explore scaling, integration with three-dimensional systems, and translation to applied settings such as soft robotics or adaptive materials.
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