Author summary Living organisms build their bodies through morphogenesis, during which cells autonomously arrange themselves into functional structures such as sheets, tubes, and spheres. From simple monolayered spheres to complex multilayered tissues organized by adhesion, it remains unclear how such diverse forms arise. Here, we mathematically modeled a population of proliferating cells governed only by two microscopic factors: the polarity strength of the cell and the time scale at which polarity is regulated by cell-cell contact. Surprisingly, we found that this minimal model reproduces five basic morphological types observed in living embryos, including monolayer/multilayer structures and two distinct modes of cavity formation: by wrapping around or by inflating from the inside. Systematic simulations revealed that these macroscale outcomes are determined solely by two parameters controlling polarity strength and its regulation, suggesting that simple physical rules underlie diverse developmental architectures. Analysis of the model uncovers phase transitions between the five morphogenetic types and reveals how varying polarity and adhesion can recapitulate features of real embryogenesis. Our work proposes a unified framework that connects microscopic polarity mechanics to diverse developmental morphologies and provides a foundation for future applications in organoid design and tissue engineering.
The investigation of biological conductivity has evolved from its classical foundation based on ionic fluxes underpinning cardiac and neuronal excitability to a multifaceted regulator of cellular physiology. Traditional approaches for probing electrical events in living matter focused largely on action potentials recording. However, bioelectricity in non-excitable cells governs key phenomena, including developmental patterning, tissue homeostasis, and disease progression. Pioneering studies implicated endogenous bioelectrics in many aspects of morphogenesis, wound healing, regeneration, and cancer. Early findings laid the groundwork for viewing bioelectricity as a means to influence cell fate, cell cycle progression, differentiation, and senescence. More recently, spatial variations in membrane potential within tumor microenvironments were found to correlate with metastatic potential. In parallel, substantial breakthroughs have been achieved in designing advanced bioelectrical interfaces for the study of neuronal networks and cardiac function. This perspective bridges the engineering and biological domains by examining how such technologies might enable new insights into non-excitable cell electrical events at different scales of operation to ultimately manipulate cellular pathways in cancer reprogramming, anti-aging interventions, and gene expression modulation.
Rxiv mechanobio