Ghosh Rikhia, Satarifard Vahid, Grafmüller Andrea, Lipowsky Reinhard
Theory & Biosystems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
ACS Nano. 2021 Apr 27;15(4):7237-7248. doi: 10.1021/acsnano.1c00525. Epub 2021 Apr 5.
Membrane budding and fission are essential cellular processes that produce new membrane compartments during cell and organelle division, for intracellular vesicle trafficking as well as during endo- and exocytosis. Such morphological transformations have also been observed for giant lipid vesicles with a size of many micrometers. Here, we report budding and fission processes of lipid nanovesicles with a size below 50 nm. We use coarse-grained molecular dynamics simulations, by which we can visualize the morphological transformations of individual vesicles. The budding and fission processes are induced by low concentrations of small solutes that absorb onto the outer leaflets of the vesicle membranes. In addition to the solute concentration, we identify the solvent conditions as a second key parameter for these processes. For solvent conditions, the budding of a nanovesicle can be controlled by reducing the vesicle volume for constant solute concentration or by increasing the solute concentration for constant vesicle volume. After the budding process is completed, the budded vesicle consists of two membrane subcompartments which are connected by a closed membrane neck. The budding process is reversible as we demonstrate explicitly by reopening the closed neck. For solvent conditions, on the other hand, we observe two unexpected morphological transformations of nanovesicles. Close to the binodal line, at which the aqueous solution undergoes phase separation, the vesicle exhibits recurrent shape changes with closed and open membrane necks, reminiscent of flickering fusion pores (kiss-and-run) as observed for synaptic vesicles. As we approach the binodal line even closer, the recurrent shape changes are truncated by the fission of the membrane neck which leads to the division of the nanovesicle into two daughter vesicles. In this way, our simulations reveal a nanoscale mechanism for the budding and fission of nanovesicles, a mechanism that arises from the interplay between membrane elasticity and solute-mediated membrane adhesion.
膜出芽和裂变是细胞的基本过程，在细胞和细胞器分裂过程中产生新的膜区室，用于细胞内囊泡运输以及胞吞和胞吐过程。这种形态转变在尺寸达数微米的巨型脂质囊泡中也有观察到。在此，我们报告了尺寸小于50 nm的脂质纳米囊泡的出芽和裂变过程。我们使用粗粒度分子动力学模拟，通过这种模拟我们可以可视化单个囊泡的形态转变。出芽和裂变过程由低浓度的小溶质诱导，这些溶质吸附在囊泡膜的外小叶上。除了溶质浓度外，我们还确定溶剂条件是这些过程的第二个关键参数。对于溶剂条件，纳米囊泡的出芽可以通过在溶质浓度恒定的情况下减小囊泡体积或在囊泡体积恒定的情况下增加溶质浓度来控制。出芽过程完成后，出芽的囊泡由两个通过封闭的膜颈连接的膜亚区室组成。正如我们通过重新打开封闭的颈明确证明的那样，出芽过程是可逆的。另一方面，对于溶剂条件，我们观察到纳米囊泡的两种意外形态转变。在接近双节线（此时水溶液发生相分离）时，囊泡表现出具有封闭和开放膜颈的反复形状变化，让人联想到突触囊泡中观察到的闪烁融合孔（吻-跑）。当我们更接近双节线时，反复的形状变化被膜颈的裂变截断，这导致纳米囊泡分裂成两个子囊泡。通过这种方式，我们的模拟揭示了纳米囊泡出芽和裂变的纳米级机制，该机制源于膜弹性和溶质介导的膜粘附之间的相互作用。
