Edwards D A, Gooch K J, Zhang I, McKinley G H, Langer R
Department of Chemical Engineering, Pennsylvania State University, University Park, 16802, USA.
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1786-91. doi: 10.1073/pnas.93.5.1786.
A theory of the mechanical origins of receptor-mediated endocytosis shows that a spontaneous membrane complex formation can provide the stimulus for a local membrane motion toward the cytosol. This motion is identified with a nucleation stage of receptor-mediated endocytosis. When membrane complexes cluster, membrane deformation is predicted to be most rapid. The rate of growth of membrane depressions depends upon the relative rates of approach of aqueous cytosolic and extracellular fluids toward the cell membrane. With cytosolic and extracellular media characterized by apparent viscosities, the rate of growth of membrane depressions is predicted to increase as the extracellular viscosity nears the apparent viscosity of the cytosol and then to decrease when the extracellular viscosity exceeds that of the cytosol. To determine whether these trends would be apparent in the overall endocytosis rate constant, an experimental study of transferrin-mediated endocytosis in two different cell lines was conducted. The experimental results reveal the same dependence of internalization rate on extracellular viscosity as predicted by the theory. These and other comparisons with experimental data suggest that the nucleation stage of receptor-mediated endocytosis is important in the overall endocytosis process.
一种关于受体介导的内吞作用的机械起源理论表明,自发的膜复合物形成可以为局部膜向细胞质溶胶的运动提供刺激。这种运动被认为是受体介导的内吞作用的成核阶段。当膜复合物聚集时,预计膜变形最为迅速。膜凹陷的生长速率取决于细胞质溶胶和细胞外液向细胞膜靠近的相对速率。在以表观粘度表征细胞质溶胶和细胞外介质的情况下,预计膜凹陷的生长速率会随着细胞外粘度接近细胞质溶胶的表观粘度而增加,而当细胞外粘度超过细胞质溶胶的表观粘度时则会降低。为了确定这些趋势在整体内吞速率常数中是否明显,对两种不同细胞系中转铁蛋白介导的内吞作用进行了实验研究。实验结果揭示了内化速率对细胞外粘度的依赖性与该理论预测的相同。这些以及与实验数据的其他比较表明,受体介导的内吞作用的成核阶段在整个内吞过程中很重要。