Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell’s response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on G-protein-coupled receptors (GPCRs), the widest group of transmembrane proteins in animals, which regulate specific cell processes through chemical signalling pathways involving a synergistic balance between the cyclic Adenosine Monophosphate (cAMP) produced by active GPCRs in the intracellular environment and its efflux, mediated by the Multidrug Resistance Proteins (MRPs) transporters. This paper develops a multiphysics approach based on the interplay among energetics, multiscale geometrical changes and mass balance of species, i.e. active GPCRs and MRPs, including diffusion and kinetics of binding and unbinding. Because the obtained energy depends upon both the kinematics and the changes of species densities, balance of mass and of linear momentum are coupled and govern the space-time evolution of the cell membrane. The mechanobiology involving remodelling and change of lipid ordering of the cell membrane allows to predict dynamics of transporters and active receptors –in full agreement with experimentally observed cAMP levels– and how the latter trigger rafts formation and cluster on such sites. Within the current scientific debate on Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and on the basis of the ascertained fact that lipid rafts often serve as an entry port for viruses, it is felt that approaches accounting for strong coupling among mechanobiological aspects could even turn helpful in better understanding membrane-mediated phenomena such as COVID-19 virus-cell interaction.

不同类型的配体结合受体聚集在增厚的细胞膜岛（即脂筏）上是一种实验观察到的现象。尽管它对细胞反应的影响已被深入研究，但配体结合过程中涉及活性受体和周围脂质膜的机械过程和多物理场之间的耦合作用尚不清楚。具体来说，这项工作的重点是G 蛋白偶联受体(GPCR)，这是动物中最广泛的跨膜蛋白，它通过涉及所产生的环磷酸腺苷(cAMP)之间的协同平衡的化学信号传导途径来调节特定的细胞过程。细胞内环境中的活性 GPCR 及其外流，由多药耐药蛋白(MRP) 转运蛋白介导。本文开发了一种基于能量学、多尺度几何变化和物质质量平衡（即活性 GPCR 和 MRP）之间相互作用的多物理场方法，包括扩散以及结合和解离动力学。由于获得的能量取决于运动学和物种密度的变化，因此质量平衡和线性动量平衡耦合并控制细胞膜的时空演化。涉及细胞膜脂质排序的重塑和改变的机械生物学允许预测转运蛋白和活性受体的动态——与实验观察到的 cAMP 水平完全一致——以及后者如何触发筏的形成和在这些位点上的聚集。在当前关于严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的科学辩论中，基于脂筏经常作为病毒的入口这一已确定的事实，人们认为，解释机械生物学之间强耦合的方法这些方面甚至可能有助于更好地理解膜介导的现象，例如 COVID-19 病毒与细胞的相互作用。