Bottacchiari Matteo, Gallo Mirko, Bussoletti Marco, Casciola Carlo M
Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, via Antonio Scarpa 16, Rome 00161, Italy.
Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, via Eudossiana 18, Rome 00184, Italy.
PNAS Nexus. 2024 Jul 25;3(8):pgae300. doi: 10.1093/pnasnexus/pgae300. eCollection 2024 Aug.
Topological transitions of lipid membranes are ubiquitous in key biological processes for cell life, like neurotransmission, fertilization, morphogenesis, and viral infections. Despite this, they are not well understood due to their multiscale nature, which limits the use of molecular models and calls for a mesoscopic approach such as the celebrated Canham-Helfrich one. Unfortunately, such a model cannot handle topological transitions, hiding the crucial involved forces and the appearance of the experimentally observed hemifused intermediates. In this work, we describe the membrane as a diffuse interface preserving the Canham-Helfrich elasticity. We show that pivotal features of the hemifusion pathway are captured by this mesoscopic approach, e.g. a (meta)stable hemifusion state and the fusogenic behavior of negative monolayer spontaneous curvatures. The membrane lateral stress profile is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular models findings. Insights into the fusogenic mechanism are reported and discussed.
脂膜的拓扑转变在细胞生命的关键生物过程中普遍存在，如神经传递、受精、形态发生和病毒感染。尽管如此，由于其多尺度性质，人们对它们的了解并不充分，这限制了分子模型的应用，并需要一种介观方法，如著名的Canham-Helfrich方法。不幸的是，这样的模型无法处理拓扑转变，掩盖了关键的相关作用力以及实验观察到的半融合中间体的出现。在这项工作中，我们将膜描述为一个保留Canham-Helfrich弹性的扩散界面。我们表明，这种介观方法捕捉到了半融合途径的关键特征，例如一个（亚）稳定的半融合状态以及负单层自发曲率的融合行为。膜的侧向应力分布作为弹性刚度的函数进行计算，得出了分子模型结果的粗粒度版本。报告并讨论了对融合机制的见解。
