CFisUC, Department of Physics, University of Coimbra, Coimbra, Portugal.
Sci Rep. 2022 Jun 2;12(1):9206. doi: 10.1038/s41598-022-13281-3.
A sound theory of biological organization is clearly missing for a better interpretation of observational results and faster progress in understanding life complexity. The availability of such a theory represents a fundamental progress in explaining both normal and pathological organism development. The present work introduces a computational implementation of some principles of a theory of organism development, namely that the default state of cells is proliferation and motility, and includes the principle of variation and organization by closure of constraints. In the present model, the bioelectric context of cells and tissue is the field responsible for organization, as it regulates cell proliferation and the level of communication driving the system's evolution. Starting from a depolarized (proliferative) cell, the organism grows to a certain size, limited by the increasingly polarized state after successive proliferation events. The system reaches homeostasis, with a depolarized core (proliferative cells) surrounded by a rim of polarized cells (non-proliferative in this condition). This state is resilient to cell death (random or due to injure) and to limited depolarization (potentially carcinogenic) events. Carcinogenesis is introduced through a localized event (a spot of depolarized cells) or by random depolarization of cells in the tissue, which returns cells to their initial proliferative state. The normalization of the bioelectric condition can reverse this out-of-equilibrium state to a new homeostatic one. This simplified model of embryogenesis, tissue organization and carcinogenesis, based on non-excitable cells' bioelectric properties, can be made more realistic with the introduction of other components, like biochemical fields and mechanical interactions, which are fundamental for a more faithful representation of reality. However, even a simple model can give insight for new approaches in complex systems and suggest new experimental tests, focused in its predictions and interpreted under a new paradigm.
对于更好地解释观察结果和更快地理解生命复杂性，显然缺少一个健全的生物组织理论。这种理论的出现代表了在解释正常和病理组织发育方面的根本进步。本工作介绍了一种组织发育理论的计算实现，即细胞的默认状态是增殖和运动，并包含通过约束闭合进行变异和组织的原理。在目前的模型中，细胞和组织的生物电环境是负责组织的场，因为它调节细胞增殖和驱动系统进化的通讯水平。从去极化（增殖）细胞开始，生物体生长到一定的大小，受增殖事件后细胞逐渐极化状态的限制。系统达到稳态，核心去极化（增殖细胞）被极化细胞（在这种条件下非增殖）的边缘包围。这种状态对细胞死亡（随机或因损伤）和有限的去极化（潜在致癌）事件具有弹性。通过局部事件（去极化细胞的斑点）或通过组织中细胞的随机去极化引入癌变，使细胞回到初始增殖状态。生物电条件的归一化可以将这种非平衡状态逆转到新的稳态。这种基于非兴奋细胞生物电特性的胚胎发生、组织组织和癌变的简化模型，可以通过引入其他组件（如生化场和机械相互作用）来使其更加现实，这些组件对于更真实地表示现实至关重要。然而，即使是一个简单的模型也可以为复杂系统的新方法提供见解，并提出新的实验测试，重点关注其预测，并在新范式下进行解释。
