The cell membrane organization has an essential functional role through the control of membrane receptor confinement in micro- or nanodomains. Several mechanisms have been proposed to account for these properties, although some features have remained controversial, notably the nature, size, and stability of cholesterol- and sphingolipid-rich domains or lipid rafts. Here, we probed the effective energy landscape acting on single-nanoparticle-labeled membrane receptors confined in raft nanodomains— epidermal growth factor receptor (EGFR), -toxin receptor (CPTR), and -toxin receptor (CSTR)—and compared it with hop-diffusing transferrin receptors. By establishing a new analysis pipeline combining Bayesian inference, decision trees, and clustering approaches, we systematically classified single-protein trajectories according to the type of effective confining energy landscape. This revealed the existence of only two distinct organization modalities: confinement in a quadratic energy landscape for EGFR, CPεTR, and CSαTR (A), and free diffusion in confinement domains resulting from the steric hindrance due to F-actin barriers for transferrin receptor (B).

中文翻译：

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约束能量景观分类揭示膜受体纳米组织机制


细胞膜组织通过控制微米或纳米域中的膜受体限制而发挥重要的功能作用。已经提出了几种机制来解释这些特性，尽管一些特征仍然存在争议，特别是富含胆固醇和鞘脂的结构域或脂筏的性质、大小和稳定性。在这里，我们探讨了作用于筏纳米结构域中的单纳米颗粒标记膜受体（表皮生长因子受体（EGFR）、β-毒素受体（CPTR）和β-毒素受体（CSTR））的有效能量景观，并将其与啤酒花进行比较-扩散转铁蛋白受体。通过建立结合贝叶斯推理、决策树和聚类方法的新分析流程，我们根据有效限制能量景观的类型对单蛋白轨迹进行系统分类。这揭示了仅存在两种不同的组织模式：EGFR、CPεTR 和 CSαTR 的二次能量景观中的限制 (A)，以及由于转铁蛋白受体的 F-肌动蛋白屏障造成的空间位阻而导致的限制域中的自由扩散 (B) ）。