Heteromultivalency Enhances Resolution in Cellular Mechanical Sorting.

IF 16.9 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jialu Zhang,Yihao Huang,Shuang Wan,Guihong Lin,Qi Guan,Ximing Chen,Yanling Song
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引用次数: 0

Abstract

Cells sense their microenvironment and neighboring cells by exerting finely tuned mechanical forces through receptor-ligand interactions, which shape mechanophenotypes critical to biological development, immunity, and disease. Profiling these mechanophenotypes requires ligands with variable avidities. However, conventional strategies based on discrete valency changes lack the precision for continuous modulation, limiting the resolution of subtle mechanotypic differences. Here, we introduce a bivariate strategy to construct heteromultivalent ligands that independently modulate both unit affinity and valency within a single DNA nanoscaffold. By co-assembling two aptamers with distinct binding affinities, each targeting different epitopes of the same receptor, we generate ligand architectures with tunable avidities through precise stoichiometric modulation. This strategy produces a continuous avidity spectrum, overcoming the limitations of traditional homovalent systems, which are constrained by the discrete nature of valency adjustments. These heteromultivalent ligands enhance the sensitivity of force measurements, revealing subtle mechanical differences in cells with varying epithelial cell adhesion molecule (EpCAM) expressions, and enabling efficient, sequential sorting of phenotypically similar subpopulations via simple flow rate adjustments. These findings underscore the critical importance of avidity modulation in multivalent interaction engineering and mechanical cell profiling, showcasing the advantages of molecularly assembled heteromultivalent interactions over conventional homovalent strategies.
异多价提高细胞机械分选的分辨率。
细胞通过受体-配体相互作用施加精细调节的机械力来感知其微环境和邻近细胞,从而形成对生物发育、免疫和疾病至关重要的机械表型。分析这些机械表型需要具有可变活性的配体。然而,基于离散价变化的传统策略缺乏连续调制的精度,限制了细微力学型差异的解决。在这里,我们引入了一种二元策略来构建异多价配体,这些配体可以独立调节单个DNA纳米支架内的单位亲和力和价。通过共同组装两个具有不同结合亲和力的适配体,每个适配体针对同一受体的不同表位,我们通过精确的化学计量调节产生具有可调亲和力的配体结构。这种策略产生了连续的贪婪谱,克服了传统同价系统的局限性,这些同价系统受价调整的离散性质的限制。这些异价配体增强了力测量的灵敏度,揭示了上皮细胞粘附分子(EpCAM)表达不同的细胞中细微的机械差异,并通过简单的流速调节实现了表型相似亚群的高效、顺序分选。这些发现强调了亲和度调制在多价相互作用工程和机械细胞分析中的重要性,展示了分子组装异多价相互作用相对于传统同价策略的优势。
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来源期刊
CiteScore
26.60
自引率
6.60%
发文量
3549
审稿时长
1.5 months
期刊介绍: Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.
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