Lipid sponge droplets as programmable synthetic organelles
Lipid sponge droplets as programmable synthetic organelles
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DOI：
10.1073/pnas.2004408117
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发表时间：
2020-08-04
影响因子：
11.1
通讯作者：
Devaraj, Neal K.
中科院分区：
文献类型：
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作者：
Bhattacharya, Ahanjit;Niederholtmeyer, Henrike;Devaraj, Neal K.
活细胞在被称为细胞器的各种亚细胞区室中分离分子并进行反应。空间组织对于扩展合成反应系统（包括人造细胞）的生化功能可能是必不可少的。许多研究试图利用层状膜结合囊泡来模拟细胞器的功能。然而，囊泡通常在膜上的运输受到高度限制，并且无法模仿细胞器（如内质网）中典型的致密膜网络。在这里，我们描述了基于高度稳定的非层状海绵相液滴的可编程合成细胞器，该液滴由单链半乳糖脂和非离子洗涤剂自发组装。由于其纳米孔结构，脂质海绵液滴很容易与周围环境交换物质。此外，海绵相包含密集的脂质双层网络和纳米级水通道，允许不同类别的分子根据其大小、极性和特定的结合基元进行划分。生物相关大分子的隔离可以通过在液滴中添加适当的功能化两亲体来编程。我们证明液滴可以容纳功能性可溶性和跨膜蛋白，允许酶和底物的共定位和浓度，以提高反应速率。液滴保护结合蛋白免受蛋白酶的侵害，这些相互作用可以被设计成可逆的和光学控制的。我们的研究结果表明，脂质海绵液滴可以很容易地将富含膜的环境和自组装的空间组织与生化反应系统整合在一起。
Living cells segregate molecules and reactions in various subcellular compartments known as organelles. Spatial organization is likely essential for expanding the biochemical functions of synthetic reaction systems, including artificial cells. Many studies have attempted to mimic organelle functions using lamellar membrane-bound vesicles. However, vesicles typically suffer from highly limited transport across the membranes and an inability to mimic the dense membrane networks typically found in organelles such as the endoplasmic reticulum. Here, we describe programmable synthetic organelles based on highly stable nonlamellar sponge phase droplets that spontaneously assemble from a single-chain galactolipid and nonionic detergents. Due to their nanoporous structure, lipid sponge droplets readily exchange materials with the surrounding environment. In addition, the sponge phase contains a dense network of lipid bilayers and nanometric aqueous channels, which allows different classes of molecules to partition based on their size, polarity, and specific binding motifs. The sequestration of biologically relevant macromolecules can be programmed by the addition of suitably functionalized amphiphiles to the droplets. We demonstrate that droplets can harbor functional soluble and transmembrane proteins, allowing for the colocalization and concentration of enzymes and substrates to enhance reaction rates. Droplets protect bound proteins from proteases, and these interactions can be engineered to be reversible and optically controlled. Our results show that lipid sponge droplets permit the facile integration of membrane-rich environments and self-assembling spatial organization with biochemical reaction systems.