Integrating Tissue and Cytoplasmic Rigidity Transitions During Morphogenesis

Multicellular organisms generate organizational complexity through morphogenesis, in which mechanical forces orchestrate the movements and deformations of cells and tissues, while chemical signals regulate the molecular events that generate and coordinate these forces. One common denominator that is critical both for mechanics and biochemistry is material property. Material properties define how materials deform or rearrange under applied forces, and how rapidly molecules interact or spread in space and time. Notably, at the two length scales that are highly relevant to multicellular morphogenesis-tissue and cytoplasmic-material properties undergo rigidity transitions. For example, tissue structures transition between fluid-like and solid-like states, while cytoplasm undergoes changes in the degrees of crowdedness and diffusivity. These transitions in space and time, as well as their underlying mechanisms, have emerged as a crucial area of research for the understanding of morphogenesis. However, tissue-scale and cytoplasmic transitions have thus far been studied primarily in separate settings designed specifically for each length scale, even though tissue properties typically arise from cellular and cytoplasmic processes-such as cell-cell adhesion, cell motility, membrane/cortical tension, and intracellular signaling, while cells themselves operate within tissues, responding to mechanical and chemical signals that spread across them. Here we review the mechanisms controlling rigidity transitions at both scales and propose an integrated, multi-scale perspective, in which we explore plausible feedback mechanisms that can link the two scales. By bridging this conceptual gap, we aim to forecast new biological mechanisms that control morphogenesis beyond the physical principles governing rigidity transitions in inert systems.