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Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury
Science ( IF 56.9 ) Pub Date : 2021-11-12 , DOI: 10.1126/science.abh3602
Z Álvarez 1, 2 , A N Kolberg-Edelbrock 1, 3 , I R Sasselli 1, 4 , J A Ortega 1, 5 , R Qiu 1, 4 , Z Syrgiannis 1, 4 , P A Mirau 6 , F Chen 1 , S M Chin 1, 4 , S Weigand 7 , E Kiskinis 1, 5 , S I Stupp 1, 2, 3, 4, 8
Affiliation  

The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor β1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. We hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.

中文翻译:

具有增强的超分子运动的生物活性支架促进脊髓损伤的恢复

已知通过模拟蛋白质的合成分子支架向细胞发出信号在组织再生中是有效的。在这里,我们描述了包含两个不同信号的肽两亲超分子聚合物,并在严重脊髓损伤的小鼠模型中对其进行了测试。一个信号激活跨膜受体 β1-整合素,第二个信号激活碱性成纤维细胞生长因子 2 受体。通过突变非生物活性域中两亲性单体的肽序列,我们加强了支架原纤维内分子的运动。这导致血管生长、轴突再生、髓鞘形成、运动神经元存活、神经胶质增生减少和功能恢复的显着差异。我们假设可以通过调整其内部运动来优化由分子集合发出的细胞信号。
更新日期:2021-11-12
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