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通过工程化整合素配体组装来控制细胞迁移。

Control cell migration by engineering integrin ligand assembly.

机构信息

Active Soft Matter Group, CAS Songshan Lake Materials Laboratory, Dongguan, China.

Bioinspired Soft Matter Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.

出版信息

Nat Commun. 2022 Aug 25;13(1):5002. doi: 10.1038/s41467-022-32686-2.

Abstract

Advances in mechanistic understanding of integrin-mediated adhesion highlight the importance of precise control of ligand presentation in directing cell migration. Top-down nanopatterning limited the spatial presentation to sub-micron placing restrictions on both fundamental study and biomedical applications. To break the constraint, here we propose a bottom-up nanofabrication strategy to enhance the spatial resolution to the molecular level using simple formulation that is applicable as treatment agent. Via self-assembly and co-assembly, precise control of ligand presentation is succeeded by varying the proportions of assembling ligand and nonfunctional peptide. Assembled nanofilaments fulfill multi-functions exerting enhancement to suppression effect on cell migration with tunable amplitudes. Self-assembled nanofilaments possessing by far the highest ligand density prevent integrin/actin disassembly at cell rear, which expands the perspective of ligand-density-dependent-modulation, revealing valuable inputs to therapeutic innovations in tumor metastasis.

摘要

在机械理解整合素介导的黏附中取得的进展强调了精确控制配体呈现对于指导细胞迁移的重要性。自上而下的纳米图案限制了空间呈现到亚微米级,这对基础研究和生物医学应用都有限制。为了打破这种限制,我们在这里提出了一种自下而上的纳米制造策略,使用简单的配方作为处理剂,将空间分辨率提高到分子水平。通过自组装和共组装,可以通过改变组装配体和非功能肽的比例来精确控制配体的呈现。组装的纳米纤维通过改变幅度来发挥对细胞迁移的增强或抑制作用,从而实现多种功能。自组装纳米纤维具有迄今为止最高的配体密度,可以防止整合素/肌动蛋白在细胞后部的解体,这扩大了配体密度依赖性调节的视角,为肿瘤转移的治疗创新提供了有价值的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d280/9411606/667ebb734f64/41467_2022_32686_Fig1_HTML.jpg

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