Intrinsically disordered proteins (IDPs) exhibit molecular-level conformational dynamics that are functionally harnessed across a wide range of fascinating biological phenomena. The low sequence complexity of IDPs has led to the design and development of intrinsically-disordered protein polymers (IDPPs), a class of engineered repeat IDPs with stimuli-responsive properties. The perfect repetitive architecture of IDPPs allows for repeat-level encoding of tunable protein functionality. Designer IDPPs can be modeled on endogenous IDPs or engineered de novo as protein polymers with dual biophysical and biological functionality. Their properties can be rationally tailored to access enigmatic IDP biology and to create programmable smart biomaterials. With the goal of inspiring the bioengineering of multifunctional IDP-based materials, here we synthesize recent multidisciplinary progress in programming and exploiting the bio-functionality of IDPPs and IDPP-containing proteins. Collectively, expanding beyond the traditional sequence space of extracellular IDPs, emergent sequence-level control of IDPP functionality is fueling the bioengineering of self-assembling biomaterials, advanced drug delivery systems, tissue scaffolds, and biomolecular condensates —genetically encoded organelle-like structures. Looking forward, we emphasize open challenges and emerging opportunities, arguing that the intracellular behaviors of IDPPs represent a rich space for biomedical discovery and innovation. Combined with the intense focus on IDP biology, the growing landscape of IDPPs and their biomedical applications set the stage for the accelerated engineering of high-value biotechnologies and biomaterials.

中文翻译：

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本质无序蛋白质聚合物的可编程性和生物医学用途


本质无序蛋白 (IDP) 表现出分子水平的构象动力学，可在多种令人着迷的生物现象中发挥作用。 IDP 的低序列复杂性导致了本质无序蛋白质聚合物 (IDPP) 的设计和开发，这是一类具有刺激响应特性的工程重复 IDP。 IDPP 的完美重复架构允许对可调蛋白质功能进行重复级编码。设计师 IDPP 可以在内源性 IDP 上建模，也可以从头设计为具有双重生物物理和生物功能的蛋白质聚合物。它们的特性可以合理定制，以获取神秘的 IDP 生物学并创建可编程智能生物材料。为了激发基于 IDP 的多功能材料的生物工程，我们在这里综合了 IDPP 和含 IDPP 蛋白质的编程和生物功能开发方面的最新多学科进展。总的来说，IDPP 功能的新兴序列水平控制超越了细胞外 IDP 的传统序列空间，正在推动自组装生物材料、先进药物输送系统、组织支架和生物分子凝聚体（基因编码的细胞器样结构）的生物工程。展望未来，我们强调开放的挑战和新兴的机遇，认为 IDPP 的细胞内行为代表了生物医学发现和创新的丰富空间。结合对 IDP 生物学的高度关注，IDPP 及其生物医学应用的不断发展为高价值生物技术和生物材料的加速工程奠定了基础。