Heuberger Lukas, Korpidou Maria, Guinart Ainoa, Doellerer Daniel, López Diego Monserrat, Schoenenberger Cora-Ann, Milinkovic Daela, Lörtscher Emanuel, Feringa Ben L, Palivan Cornelia G
Department of Chemistry, University of Basel, Basel, 4002, Switzerland.
Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, AG Groningen, 9747, The Netherlands.
Adv Mater. 2025 Jan;37(3):e2413981. doi: 10.1002/adma.202413981. Epub 2024 Nov 3.
Deciphering inter- and intracellular signaling pathways is pivotal for understanding the intricate communication networks that orchestrate life's dynamics. Communication models involving bottom-up construction of protocells are emerging but often lack specialized compartments sufficiently robust and hierarchically organized to perform spatiotemporally defined signaling. Here, the modular construction of communicating polymer-based protocells designed to mimic the transduction of information in retinal photoreceptors is presented. Microfluidics is used to generate polymeric protocells subcompartmentalized by specialized artificial organelles. In one protocell population, light triggers artificial organelles with membrane-embedded photoresponsive rotary molecular motors to set off a sequence of reactions starting with the release of encapsulated signaling molecules into the lumen. Intercellular communication is mediated by signal transfer across membranes to protocells containing catalytic artificial organelles as subcompartments, whose signal conversion can be modulated by environmental calcium. Signal propagation also requires selective permeability of the diverse compartments. By segregating artificial organelles in distinct protocells, a sequential chain of reactions mediating intercellular communication is created that is further modulated by adding extracellular messengers. This connective behavior offers the potential for a deeper understanding of signaling pathways and faster integration of proto- and living cells, with the unique advantage of controlling each step by bio-relevant signals.
破译细胞间和细胞内信号通路对于理解协调生命动态的复杂通信网络至关重要。涉及自下而上构建原始细胞的通信模型正在兴起,但通常缺乏足够强大且层次化组织的专门隔室来执行时空定义的信号传导。在此,展示了基于聚合物的通信原始细胞的模块化构建,其旨在模拟视网膜光感受器中的信息转导。微流控技术用于生成由专门的人工细胞器进行亚分隔的聚合物原始细胞。在一个原始细胞群体中,光触发带有膜嵌入光响应旋转分子马达的人工细胞器,引发一系列反应,首先是将封装的信号分子释放到内腔中。细胞间通信由信号跨膜转移到含有催化人工细胞器作为亚隔室的原始细胞介导,其信号转换可由环境钙调节。信号传播还需要不同隔室的选择性通透性。通过在不同的原始细胞中分离人工细胞器,创建了介导细胞间通信的连续反应链,通过添加细胞外信使可对其进行进一步调节。这种连接行为为更深入理解信号通路以及原始细胞与活细胞的更快整合提供了潜力,具有通过生物相关信号控制每个步骤的独特优势。