Complete budding and asymmetric division of primitive model cells to produce daughter vesicles with different interior and membrane compositions.
Complete budding and asymmetric division of primitive model cells to produce daughter vesicles with different interior and membrane compositions.
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原始模型细胞的完整萌芽和不对称分裂，以产生具有不同内部和膜组成的子囊泡。
DOI：
10.1021/ja202406v
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发表时间：
2011-06-22
影响因子：
15
通讯作者：
Keating, Christine D.
中科院分区：
文献类型：
--
作者：
Andes-Koback, Meghan;Keating, Christine D.
细胞不对称分裂是生物学中普遍存在的现象，对细胞的分化和发育起着至关重要的作用。单细胞生物体经常被用作模型系统，以了解细胞分裂过程中不对称的起源和后果。尽管与哺乳动物细胞相比，这些细胞是基本的，但它们已经相当复杂。我们报道了非常简单的无生命模型细胞的完全发芽和不对称分裂，以产生内部和膜成分在化学上都不同的子囊泡。我们的模型细胞基于巨大的脂泡(GV)，10-30μm包裹着聚乙二醇/葡聚糖双水相系统(ATPS)，作为拥挤和分隔的细胞质模拟物。三元类脂组成被用来在膜中提供共存的微米级液体无序(LD)和液体有序(LO)结构域。当向外添加蔗糖以提供更高的渗透压时，含有ATPS的囊泡形成芽，这样它们不仅在形态上不对称，而且在内部和膜成分上都变得不对称。渗透压的进一步增加促使形成两个化学上不同的子囊泡，在某些情况下，它们由脂质纳米管连接(完全发芽)，而在另一些情况下，它们不是(分裂)。在所有情况下，分离发生在水-水相边界，使得一个子囊泡包含富含聚乙二醇水相，而另一个子囊泡包含富含葡聚糖的水相。聚乙二醇化的脂类定位于LO结构域，导致该膜结构域在分裂前优先覆盖富含聚乙二醇的芽，随后覆盖富含聚乙二醇的子囊泡。改变脂类的摩尔比会导致LO或LD膜结构域的表面积过大，从而在分裂时，这一过剩部分由其中一个子囊泡继承。在某些情况下，可以在这些子囊泡中诱导第二代水相分离和萌发。简单的自组装模型细胞的不对称分裂产生了含有不同蛋白质浓度和脂肪成分的子囊泡，这是简单分子组装可能出现的看似复杂的行为的一个例子。这些分区的和不对称划分的含ATPS的GV可以作为一个试验台，用于研究空间和组织线索在不对称细胞分裂和遗传中的可能作用。
Asymmetric cell division is common in biology and plays critical roles in differentiation and development. Unicellular organisms are often used as model systems for understanding the origins and consequences of asymmetry during cell division. Although basic as compared to mammalian cells, these are already quite complex. We report complete budding and asymmetric fission of very simple nonliving model cells to produce daughter vesicles that are chemically distinct in both interior and membrane compositions. Our model cells are based on giant lipid vesicles (GVs, 10–30 μm) encapsulating a polyethylene glycol (PEG)/dextran aqueous two-phase system (ATPS) as a crowded and compartmentalized cytoplasm mimic. Ternary lipid compositions were used to provide coexisting micrometer-scale liquid disordered (Ld) and liquid ordered (Lo) domains in the membranes. ATPS-containing vesicles formed buds when sucrose was added externally to provide increased osmotic pressure, such that they became not only morphologically asymmetric but also asymmetric in both their interior and their membrane compositions. Further increases in osmolality drove formation of two chemically distinct daughter vesicles, which were in some cases connected by a lipid nanotube (complete budding), and in others were not (fission). In all cases, separation occurred at the aqueous–aqueous phase boundary, such that one daughter vesicle contained the PEG-rich aqueous phase and the other contained the dextran-rich aqueous phase. PEGylated lipids localized in the Lo domain resulted in this membrane domain preferentially coating the PEG-rich bud prior to division, and subsequently the PEG-rich daughter vesicle. Varying the mole ratio of lipids resulted in excess surface area of Lo or Ld membrane domains such that, upon division, this excess portion was inherited by one of the daughter vesicles. In some cases, a second “generation” of aqueous phase separation and budding could be induced in these daughter vesicles. Asymmetric fission of a simple self-assembled model cell, with production of daughter vesicles that harbored different protein concentrations and lipid compositions, is an example of the seemingly complex behavior possible for simple molecular assemblies. These compartmentalized and asymmetrically dividing ATPS-containing GVs could serve as a test bed for investigating possible roles for spatial and organizational cues in asymmetric cell division and inheritance.
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