Woods Ben, Thompson Katherine C, Szita Nicolas, Chen Shu, Milanesi Lilia, Tomas Salvador
Department of Biological Sciences and Institute of Structural and Molecular Biology, Birkbeck, University of London Malet Street London WC1E 7HX UK.
Department of Biochemical Engineering, University College London, Bernard Katz Building Gordon Street London WC1H 0AH UK.
Chem Sci. 2023 Feb 15;14(10):2616-2623. doi: 10.1039/d2sc05747f. eCollection 2023 Mar 8.
In living organisms most chemical reactions take place within the confines of lipid-membrane bound compartments, while confinement within the bounds of a lipid membrane is thought to be a key step in abiogenesis. In previous work we demonstrated that confinement in the aqueous cavity of a lipid vesicle affords protection against hydrolysis, a phenomenon that we term here confinement effect ( ) and that we attributed to the interaction with the lipid membrane. Here, we show that both the size and the shape of the cavity of the vesicle modulate the . We link this observation to the packing of the lipid following changes in membrane curvature, and formulate a mathematical model that relates the to the radius of a spherical vesicle and the packing parameter of the lipids. These results suggest that the shape of the compartment where a molecule is located plays a major role in controlling the chemical reactivity of non-enzymatic reactions. Moreover, the mathematical treatment we propose offers a useful tool for the design of vesicles with predictable reaction rates of the confined molecules, , drug delivery vesicles with confined prodrugs. The results also show that a crude form of signal transduction, devoid of complex biological machinery, can be achieved by any external stimuli that drastically changes the structure of the membrane, like the osmotic shocks used in the present work.
在活生物体中，大多数化学反应发生在脂质膜包裹的隔室内，而脂质膜包裹被认为是生命起源的关键步骤。在之前的工作中，我们证明了脂质囊泡水腔中的包裹作用能提供抗水解保护，我们在此将这种现象称为包裹效应，并将其归因于与脂质膜的相互作用。在这里，我们表明囊泡腔的大小和形状都会调节包裹效应。我们将这一观察结果与膜曲率变化后脂质的堆积联系起来，并建立了一个数学模型，将包裹效应与球形囊泡的半径和脂质的堆积参数联系起来。这些结果表明，分子所处隔室的形状在控制非酶促反应的化学反应性方面起着主要作用。此外，我们提出的数学处理方法为设计具有可预测的被包裹分子反应速率的囊泡，即具有被包裹前药的药物递送囊泡，提供了一个有用的工具。结果还表明，通过任何能大幅改变膜结构的外部刺激，如本工作中使用的渗透压冲击，都可以实现一种没有复杂生物机制的原始形式的信号转导。
