坪田 健一

Abstract Living tissues exhibit complex mechanical properties, including viscoelastic and elastoplastic responses, that are crucial for regulating cell behaviors and tissue deformations. Despite their significance, the intricate properties of three-dimensional (3D) multicellular tissues are not well understood and are inadequately implemented in biomaterial engineering. To address this gap, we developed a numerical method to analyze the dynamic properties of multicellular tissues using a 3D vertex model framework. By focusing on 3D tissues composed of confluent homogeneous cells, we characterized their properties in response to various deformation magnitudes and time scales. Stress relaxation tests revealed that large deformations initially induced relaxation in the shapes of individual cells. This process is amplified by subsequent transient cell rearrangements, homogenizing cell shapes and leading to tissue fluidization. Additionally, dynamic viscoelastic analyses showed that tissues exhibited strain softening and hysteresis during large deformations. Interestingly, this strain softening originates from multicellular structures independent of cell rearrangement, while hysteresis arises from cell rearrangement. Moreover, tissues exhibit elastoplastic responses over the long term, which are well represented by the Ramberg–Osgood model. These findings highlight the characteristic properties of multicellular tissues emerging from their structures and rearrangements, especially during long-term large deformations. The developed method offers a new approach to uncover the dynamic nature of 3D tissue mechanics and could serve as a technical foundation for exploring tissue mechanics and advancing biomaterial engineering.

A numerical simulation was carried out to investigate the blood flow behavior (i.e., flow rate and pressure) and coupling of a renal vascular network and the myogenic response to various conditions. A vascular segment and an entire kidney vascular network were modeled by assuming one single vessel as a straight pipe whose diameter was determined by Murray’s law. The myogenic response was tested on individual AA (afferent artery)–GC (glomerular capillaries)–EA (efferent artery) systems, thereby regulating blood flow throughout the vascular network. Blood flow in the vascular structure was calculated by network analysis based on Hagen–Poiseuille’s law to various boundary conditions. Simulation results demonstrated that, in the vascular segment, the inlet pressure Pinlet and the vascular structure act together on the myogenic response of each individual AA–GC–EA subsystem, such that the early-branching subsystems in the vascular network reached the well-regulated state first, with an interval of the inlet as Pinlet = 10.5–21.0 kPa, whereas the one that branched last exhibited a later interval with Pinlet = 13.0–24.0 kPa. In the entire vascular network, in contrast to the Pinlet interval (13.0–20.0 kPa) of the unified well-regulated state for all AA–GC–EA subsystems of the symmetric model, the asymmetric model exhibited the differences among subsystems with Pinlet ranging from 12.0–17.0 to 16.0–20.0 kPa, eventually achieving a well-regulated state of 13.0–18.5 kPa for the entire kidney. Furthermore, when Pinlet continued to rise (e.g., 21.0 kPa) beyond the vasoconstriction range of the myogenic response, high glomerular pressure was also related to vascular structure, where PGC of early-branching subsystems was 9.0 kPa and of late-branching one was 7.5 kPa. These findings demonstrate how the myogenic response regulates renal blood flow in vascular network system that comprises a large number of vessel elements.