Program in Biophysics, Stanford University, Stanford, CA 94305, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Mol Biol. 2021 Jun 11;433(12):166837. doi: 10.1016/j.jmb.2021.166837. Epub 2021 Feb 1.
Protein phase separation has emerged as a novel paradigm to explain the biogenesis of membraneless organelles and other so-called biomolecular condensates. While the implication of this physical phenomenon within cell biology is providing us with novel ways for understanding how cells compartmentalize biochemical reactions and encode function in such liquid-like assemblies, the newfound appreciation of this process also provides immense opportunities for designing and sculpting biological matter. Here, we propose that understanding the cell's instruction manual of phase separation will enable bioengineers to begin creating novel functionalized biological materials and unprecedented tools for synthetic biology. We present FASE as the synthesis of the existing sticker-spacer framework, which explains the physical driving forces underlying phase separation, with quintessential principles of Scandinavian design. FASE serves both as a designer condensates catalogue and construction manual for the aspiring (membraneless) biomolecular architect. Our approach aims to inspire a new generation of bioengineers to rethink phase separation as an opportunity for creating reactive biomaterials with unconventional properties and to encode novel biological function in living systems. Although still in its infancy, several studies highlight how designer condensates have immediate and widespread potential applications in industry and medicine.
蛋白质液-液相分离已成为一种新兴范例，用以解释无膜细胞器和其他所谓的生物分子凝聚物的生物发生。虽然这种物理现象在细胞生物学中的意义为我们提供了理解细胞如何分隔生化反应并在这种类似液体的组装体中编码功能的新方法，但对这一过程的新认识也为设计和塑造生物物质提供了巨大的机会。在这里，我们提出，了解细胞液-液相分离的指令手册将使生物工程师能够开始创造新型功能化生物材料和用于合成生物学的前所未有的工具。我们提出 FASE 是现有贴纸-间隔物框架的综合，它用斯堪的纳维亚设计的精髓原则来解释液-液相分离的物理驱动力。FASE 既是设计师凝聚物目录，也是有抱负的（无膜）生物分子建筑师的施工手册。我们的方法旨在激发新一代生物工程师重新思考液-液相分离，将其视为创造具有非常规性质的反应性生物材料的机会，并在活细胞系统中编码新的生物学功能。尽管它还处于起步阶段，但已有几项研究强调了设计凝聚物在工业和医学中的直接和广泛的潜在应用。
