Membrane-confined liquid-liquid phase separation toward artificial organelles

Abstract

As the basic unit of life, cells are compartmentalized microreactors with molecularly crowded microenvironments. The quest to understand the cell origin inspires the design of synthetic analogs to mimic their functionality and structural complexity. In this work, we integrate membraneless coacervate microdroplets, a prototype of artificial organelles, into a proteinosome to build hierarchical protocells that may serve as a more realistic model of cellular organization. The protocell subcompartments can sense extracellular signals, take actions in response to these stimuli, and adapt their physicochemical behaviors. The tiered protocells are also capable of enriching biomolecular reactants within the confined organelles, thereby accelerating enzymatic reactions. The ability of signal processing inside protocells allows us to design the Boolean logic gates (NOR and NAND) using biochemical inputs. Our results highlight possible exploration of protocell-community signaling and render a flexible synthetic platform to study complex metabolic reaction networks and embodied chemical computation.

Coupling Bulk Phase Separation of Disordered Proteins to Membrane Domain Formation in Molecular Simulations on a Bespoke Compute Fabric

“…Recent experiments show that phase separation of T cell proteins at the surface of giant unilamellar lipid vesicles drives lipid domain formation that in turn is able to recruit additional proteins to the domains [36]. This provides a starting point for rational design of artificial organelles [37].…”

Research progress in stimulus-responsive behaviors of artificial cells

“…Liu等人 人工细胞中, 区室化的模拟结构可以将不同种酶定位 在膜的特定区域中, 通过调控酶的空间位置来调控酶 反应速率 [49] . Mu等人 [19] 用蛋白质囊泡包裹凝聚体构 建了原始细胞. 具有pH敏感的谷氨酸衍生物和光敏的 (b) 利用葡萄糖氧化酶(GOx)、肌红蛋白(Myo)和过氧化氢酶 (Cat)进行代谢模拟的酶级联反应 [26] (网络版彩图)…”

“…将细胞作为"活体计算 机", 对生物体的细胞功能和代谢活动进行编程, 在活 细胞内引入逻辑门进行数字计算, 可能会在未来的基 于基因和基于细胞的治疗中提供新的治疗策略和生物 电子接口 [75] . 而在人工细胞中引入布尔逻辑门的研究 较少 [19,76] , 所构建的布尔逻辑门也相对较为简单. 在 参考文献…”

Pickering emulsion droplet-based biomimetic microreactors for continuous flow cascade reactions

“…The high efficiency is in part attributed to the unique multi-level compartmentalization in cells that enables them to sequester reactants/intermediates and spatially isolate incompatible species within different organelles (sub-compartments (SCs)) 11 . Motivated by the approach of nature in its realization, extensive efforts have been made to synthesize various biomimetic microreactors for executing cascade reactions, such as lipid vesicles 12 , 13 , polymersomes 14 – 17 , microcapsules 18 – 27 , coacervate droplets 28 , 29 , and proteinosomes 30 , 31 . Although encouraging progress has been achieved, most of these existing biomimetic microreactors either require relatively complex fabrication procedures or lack a proper liquid medium inside their interior, leading to either difficulty in rationally controlling the interior structures or inability to enrich/sequester reactants 32 .…”