The Fluid Mosaic Model of the Structure of Cell Membranes
The Fluid Mosaic Model of the Structure of Cell Membranes
复制标题
DOI：
10.1126/science.175.4023.720
复制
发表时间：
1972-01-01
期刊：
影响因子：
56.9
通讯作者：
NICOLSON, GL
中科院分区：
文献类型：
--
作者：
SINGER, SJ;NICOLSON, GL
本文提出了一个描述生物膜蛋白质和脂类的宏观组织和结构的流体镶嵌模型。该模型符合热力学的限制条件。在这个模型中，与膜结合的蛋白质是一组异质的球状分子，每个球状分子排列成两亲性结构，即离子和高极性基团从膜突出到水相中，而非极性基团大部分埋在膜的疏水内部。这些球状分子部分嵌入磷脂基质中。大部分磷脂被组织成不连续的流体双层，尽管一小部分脂质可以与膜蛋白特异性相互作用。因此，流体镶嵌结构在形式上类似于粘性磷脂双层溶剂中的整合蛋白质（或脂蛋白）的二维取向溶液。最近的实验与各种各样的技术和几种不同的膜系统进行了描述，所有这些都是一致的，并增加了很多细节，流体镶嵌模型。因此，似乎适当的建议可能的机制，各种膜功能和膜介导的现象，在光的模型。作为例子，实验上可检验的机制被建议为恶性转化中的细胞表面变化，以及在膜与某些特定配体的相互作用中表现出的协同效应。自从这篇文章写出来后，我们已经获得了电镜证据，证明SV 40病毒转化的小鼠成纤维细胞膜上的伴刀豆球蛋白A结合位点正如图7 B中所示的假设所预测的那样，（3 T3细胞）比正常细胞膜上的位点更加聚集。Tayloret等人的一项研究也表明，通过加入针对淋巴细胞表面免疫球蛋白分子的抗体，对淋巴细胞产生了显著的影响。抗体诱导这些表面免疫球蛋白的再分布和胞饮作用，使得在37°C下约30分钟内，表面免疫球蛋白被完全清除出膜。然而，如果二价抗体被其单价Fab片段取代，或者如果抗体实验在0°C而不是3°C下进行，则不会发生这些效应。这些和相关结果强烈表明，二价抗体在膜平面中产生表面免疫球蛋白分子的聚集，这仅在免疫球蛋白分子在膜中自由扩散时才可能发生。然后，这种聚集似乎通过某种未知的机制触发了膜组分的胞饮作用。这种膜转化在诱导对抗原的抗体应答以及在细胞分化的其他过程中可能是至关重要的。
A fluid mosaic model is presented for the gross organization and structure of the proteins and lipids of biological membranes. The model is consistent with the restrictions imposed by thermodynamics. In this model, the proteins that are integral to the membrane are a heterogeneous set of globular molecules, each arranged in anamphipathicstructure, that is, with the ionic and highly polar groups protruding from the membrane into the aqueous phase, and the nonpolar groups largely buried in the hydrophobic interior of the membrane. These globular molecules are partially embedded in a matrix of phospholipid. The bulk of the phospholipid is organized as a discontinuous, fluid bilayer, although a small fraction of the lipid may interact specifically with the membrane proteins. The fluid mosaic structure is therefore formally analogous to a two-dimensional oriented solution of integral proteins (or lipoproteins) in the viscous phospholipid bilayer solvent. Recent experiments with a wide variety of techniques and several different membrane systems are described, all of which are consistent with, and add much detail to, the fluid mosaic model. It therefore seems appropriate to suggest possible mechanisms for various membrane functions and membrane-mediated phenomena in the light of the model. As examples, experimentally testable mechanisms are suggested for cell surface changes in malignant transformation, and for cooperative effects exhibited in the interactions of membranes with some specific ligands.Note added in proof: Since this article was written, we have obtained electron microscopic evidence that the concanavalin A binding sites on the membranes of SV40 virus-transformed mouse fibroblasts (3T3 cells) are more clustered than the sites on the membranes of normal cells, as predicted by the hypothesis represented in Fig. 7B. There has also appeared a study by Tayloret al.showing the remarkable effects produced on lymphocytes by the addition of antibodies directed to their surface immunoglobulin molecules. The antibodies induce a redistribution and pinocytosis of these surface immunoglobulins, so that within about 30 minutes at 37°C the surface immunoglobulins are completely swept out of the membrane. These effects do not occur, however, if the bivalent antibodies are replaced by their univalent Fab fragments or if the antibody experiments are carried out at 0°C instead of 3°C. These and related results strongly indicate that the bivalent antibodies produce an aggregation of the surface immunoglobulin molecules in the plane of the membrane, which can occur only if the immunoglobulin molecules are free to diffuse in the membrane. This aggregation then appears to trigger off the pinocytosis of the membrane components by some unknown mechanism. Such membrane transformations may be of crucial importance in the induction of an antibody response to an antigen, as well as in other processes of cell differentiation.