Laboratoire de Physique Théorique, Université Toulouse III - Paul Sabatier, CNRS, Toulouse, France.
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UPS), Toulouse, France.
Biophys J. 2023 Jun 6;122(11):2112-2124. doi: 10.1016/j.bpj.2022.12.009. Epub 2022 Dec 7.
In cell membranes, proteins and lipids are organized into submicrometric nanodomains of varying sizes, shapes, and compositions, performing specific functions. Despite their biological importance, the detailed morphology of these nanodomains remains unknown. Not only can they hardly be observed by conventional microscopy due to their small size, but there is no full consensus on the theoretical models to describe their structuring and their shapes. Here, we use a combination of analytical calculations and Monte Carlo simulations based upon a model coupling membrane composition and shape to show that increasing protein concentration leads to an elongation of membrane nanodomains. The results are corroborated by single-particle tracking measurements on HIV receptors, whose level of expression in the membrane of specifically designed living cells can be tuned. These findings highlight that protein abundance can modulate nanodomain shape and potentially their biological function. Beyond biomembranes, this mesopatterning mechanism is of relevance in several soft-matter systems because it relies on generic physical arguments.
在细胞膜中,蛋白质和脂质组织成具有不同大小、形状和组成的亚微观纳米域,执行特定的功能。尽管它们具有重要的生物学意义,但这些纳米域的详细形态仍然未知。由于它们的体积小,不仅传统显微镜很难观察到它们,而且对于描述它们的结构和形状的理论模型也没有完全达成共识。在这里,我们使用基于结合膜组成和形状的模型的分析计算和蒙特卡罗模拟的组合,表明随着蛋白质浓度的增加,膜纳米域会变长。这些结果得到了针对 HIV 受体的单粒子跟踪测量的证实,HIV 受体在特别设计的活细胞的膜中的表达水平可以进行调节。这些发现强调了蛋白质丰度可以调节纳米域的形状,并可能调节其生物学功能。除了生物膜之外,这种介观图案形成机制在几种软物质系统中也很重要,因为它依赖于通用的物理论据。