Munaron Luca, Scianna Marco
Luca Munaron, Department of Life Sciences and Systems Biology, Centre for Nanostructured Interfaces and Surfaces, Centre for Complex Systems in Molecular Biology and Medicine, University of Torino, 10123 Torino, Italy.
World J Biol Chem. 2012 Jun 26;3(6):121-6. doi: 10.4331/wjbc.v3.i6.121.
Intracellular calcium signaling is a universal, evolutionary conserved and versatile regulator of cell biochemistry. The complexity of calcium signaling and related cell machinery can be investigated by the use of experimental strategies, as well as by computational approaches. Vascular endothelium is a fascinating model to study the specific properties and roles of calcium signals at multiple biological levels. During the past 20 years, live cell imaging, patch clamp and other techniques have allowed us to detect and interfere with calcium signaling in endothelial cells (ECs), providing a huge amount of information on the regulation of vascularization (angiogenesis) in normal and tumoral tissues. These data range from the spatiotemporal dynamics of calcium within different cell microcompartments to those in entire multicellular and organized EC networks. Beside experimental strategies, in silico endothelial models, specifically designed for simulating calcium signaling, are contributing to our knowledge of vascular physiology and pathology. They help to investigate and predict the quantitative features of proangiogenic events moving through subcellular, cellular and supracellular levels. This review focuses on some recent developments of computational approaches for proangiogenic endothelial calcium signaling. In particular, we discuss the creation of hybrid simulation environments, which combine and integrate discrete Cellular Potts Models. They are able to capture the phenomenological mechanisms of cell morphological reorganization, migration, and intercellular adhesion, with single-cell spatiotemporal models, based on reaction-diffusion equations that describe the agonist-induced intracellular calcium events.
细胞内钙信号传导是一种普遍的、进化上保守且多功能的细胞生物化学调节因子。钙信号传导及相关细胞机制的复杂性可通过实验策略以及计算方法进行研究。血管内皮是一个极具吸引力的模型，可用于在多个生物学层面研究钙信号的特定特性和作用。在过去20年中，活细胞成像、膜片钳及其他技术使我们能够检测并干扰内皮细胞（ECs）中的钙信号传导，为正常和肿瘤组织中血管生成（血管新生）的调节提供了大量信息。这些数据涵盖了从不同细胞微区室到整个多细胞且有组织的EC网络中钙的时空动态。除了实验策略，专门设计用于模拟钙信号传导的计算机内皮模型也有助于我们了解血管生理学和病理学。它们有助于研究和预测通过亚细胞、细胞和超细胞水平发生的促血管生成事件的定量特征。本综述重点关注促血管生成内皮钙信号传导计算方法的一些最新进展。特别是，我们讨论了混合模拟环境的创建，该环境结合并整合了离散的细胞Potts模型。它们能够通过基于描述激动剂诱导的细胞内钙事件的反应扩散方程的单细胞时空模型，捕捉细胞形态重组、迁移和细胞间粘附的现象学机制。
