The geometric nature of homeostatic stress in biological growth

Morphogenesis, the process of growth and shape formation in biological tissues, is driven by complex interactions between mechanical, biochemical, and genetic factors. Traditional models of biological growth often rely on the concept of homeostatic Eshelby stress, which defines an ideal target state for the growing body. Any local deviation from this state triggers growth and remodelling, aimed at restoring balance between mechanical forces and biological adaptation. Despite its relevance in the biomechanical context, the nature of homeostatic stress remains elusive, with its value and spatial distribution often chosen arbitrarily, lacking a clear biological interpretation or understanding of its connection to the lower scales of the tissue. To bring clarity on the nature of homeostatic stress, we shift the focus from Eshelby stress to growth incompatibility, a measure of geometric frustration in the tissue that is the primary source of residual stresses in the developing body. Incompatibility, which is measured by the Ricci tensor of the growth metric at the continuous level, can be potentially regulated at the cell level through the formation of appropriate networks and connections with the surrounding cells, making it a more meaningful concept than homeostatic stress as a fixed target. In this geometric perspective, achieving a homeostatic state corresponds to the establishment of a physiological level of frustration in the body, a process leading to the generation and maintenance of the mechanical stresses that are crucial to tissue functionality. While residual stress can be induced through either active contraction or differential growth, the latter is the focus of this work. In this work we present a formulation of biological growth that penalises deviations from a desired state of incompatibility, similar to the way the Einstein–Hilbert action operates in General Relativity. The proposed framework offers a clear and physically grounded approach that elucidates the regulation of size and shape, while providing a means to link cellular and tissue scales in biological systems.