Self-assembling multidomain peptide hydrogels: designed susceptibility to enzymatic cleavage allows enhanced cell migration and spreading.
Self-assembling multidomain peptide hydrogels: designed susceptibility to enzymatic cleavage allows enhanced cell migration and spreading.
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DOI：
10.1021/ja910481t
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发表时间：
2010-03-10
影响因子：
15
通讯作者：
Hartgerink JD
中科院分区：
文献类型：
--
作者：
Galler KM;Aulisa L;Regan KR;D'Souza RN;Hartgerink JD
多结构域肽是一类具有模块化 ABA 块基序的两亲性自组装肽，其中两亲性 B 块驱动自组装，而带静电的侧翼 A 块控制组装发生的条件。之前我们已经证明，仔细选择 A 和 B 块中的氨基酸可以控制自组装纤维长度和形成的水凝胶的粘弹性。在这里，我们展示了如何为生物应用设计这种肽组装器的模块化特性。通过控制纤维长度和直径、凝胶条件和粘弹性，我们可以开发适合生物应用的材料。生物功能支架超越了用于细胞递送的简单载体，它将与其携带的细胞相互作用，促进有利的细胞-基质相互作用。我们展示了通过掺入基质金属蛋白酶-2 (MMP-2) 特异性切割位点和细胞粘附基序将多结构域肽设计成生物活性变体。评估了凝胶形成和流变特性，并与相关肽水凝胶进行了比较。在凝胶减重研究中观察到胶原酶 IV 的蛋白水解降解，并通过质谱和冷冻 TEM 监测的特定 MMP-2 降解得到证实。该裂解位点与细胞粘附基序 RGD 的组合导致细胞活力增加、细胞扩散，并促进细胞迁移到水凝胶基质中。这种多域肽水凝胶的结构、机械和生物活性特性使其适合作为各种组织工程应用的可注射材料。
Multidomain Peptides are a class of amphiphilic self-assembling peptides with a modular ABA block motif in which the amphiphilic B block drives self-assembly while the flanking A blocks, which are electrostaticly charged, control the conditions under which assembly takes place. Previously we have shown that careful selection of the amino acids in the A and B blocks allow one to control the self-assembled fiber length and viscoelastic properties of formed hydrogels. Here we demonstrate how the modular nature of this peptide assembler can be designed for biological applications. With control over fiber length and diameter, gelation conditions and viscoelastic properties, we can develop suitable materials for biological applications. Going beyond a simple carrier for cell delivery, a biofunctional scaffold will interact with the cells it carries promoting advantageous cell-matrix interactions. We demonstrate the design of a multidomain peptide into a bioactive variant by incorporation of a matrix metalloprotease-2 (MMP-2) specific cleavage site and cell adhesion motif. Gel formation and rheological properties were assessed and compared to related peptide hydrogels. Proteolytic degradation by collagenase IV was observed in a gel weight loss study, and confirmed by specific MMP-2 degradation monitored by mass spectrometry and cryo-TEM. Combination of this cleavage site with the cell adhesion motif RGD resulted in increased cell viability, cell spreading, and encouraged cell migration into the hydrogel matrix. Collectively the structural, mechanical and bioactive properties of this multidomain peptide hydrogel make it suitable as an injectable material for a variety of tissue engineering applications.
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影响因子：
46.9
作者：
Turk, BE;Huang, LL;Cantley, LC
通讯作者：
Cantley, LC
影响因子：
15
作者：
Dong, He;Paramonov, Sergey E.;Hartgerink, Jeffrey D.
通讯作者：
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影响因子：
3.4
作者：
Dikovsky, Daniel;Bianco-Peled, Havazelet;Seliktar, Dror
通讯作者：
Seliktar, Dror
影响因子：
14
作者：
Almany, L;Seliktar, D
通讯作者：
Seliktar, D
DOI：
10.1073/pnas.97.12.6728
发表时间：
2000-06-06
影响因子：
11.1
作者：
Holmes, TC;de Lacalle, S;Zhang, SG
通讯作者：
Zhang, SG