Coupled Growth and Division of Model Protocell Membranes

The generation of synthetic forms of cellular life requires solutions to the problem of how biological processes such as cyclic growth and division could emerge from purely physical and chemical systems. Small unilamellar fatty acid vesicles grow when fed with fatty acid micelles and can be forced to divide by extrusion, but this artificial division process results in significant loss of protocell contents during each division cycle. Here we describe a simple and efficient pathway for model protocell membrane growth and division. The growth of large multilamellar fatty acid vesicles fed with fatty acid micelles, in a solution where solute permeation across the membranes is slow, results in the transformation of initially spherical vesicles into long thread-like vesicles, a process driven by the transient imbalance between surface area and volume growth. Modest shear forces are then sufficient to cause the thread-like vesicles to divide into multiple daughter vesicles without loss of internal contents. In an environment of gentle shear, protocell growth and division are thus coupled processes. We show that model protocells can proceed through multiple cycles of reproduction. Encapsulated RNA molecules, representing a primitive genome, are distributed to the daughter vesicles. Our observations bring us closer to the laboratory synthesis of a complete protocell consisting of a self-replicating genome and a self-replicating membrane compartment. In addition, the robustness and simplicity of this pathway suggests that similar processes might have occurred under the prebiotic conditions of the early Earth.

合成型细胞生命的构建，需要解决如下核心科学问题：如何从纯物理与化学系统中，催生出循环生长、分裂这类生物学过程。小型单膜层脂肪酸囊泡（small unilamellar fatty acid vesicles）在获取脂肪酸胶束（fatty acid micelles）后会发生生长，且可通过挤压诱导分裂，但该人工分裂过程会在每次分裂周期中造成原细胞（protocell）内容物的大量流失。本文报道了一条用于模型原细胞膜生长与分裂的简便高效途径。在溶质跨膜渗透速率较慢的溶液体系中，投喂脂肪酸胶束的大型多膜层脂肪酸囊泡（large multilamellar fatty acid vesicles）会发生生长，其初始球形囊泡会转变为长丝状囊泡，这一过程由表面积增长与体积增长之间的瞬时失衡所驱动。随后，仅需适度的剪切力（shear forces）即可使丝状囊泡分裂为多个子代囊泡，且不会造成内部内容物的流失。在温和剪切环境下，原细胞的生长与分裂便成为偶联过程。我们证实，模型原细胞可完成多轮繁殖循环，包封的RNA分子（代表原始基因组）会被分配至子代囊泡中。本研究的观测结果，使我们在实验室合成由自我复制基因组与自我复制膜区室共同构成的完整原细胞的道路上更进一步。此外，该途径的鲁棒性与简便性提示，类似过程或曾发生于早期地球的生命起源前环境（prebiotic conditions）中。