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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Two-component protein-engineered physical hydrogels for cell encapsulation
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Two-component protein-engineered physical hydrogels for cell encapsulation

机译：用于细胞包封的两组分蛋白质工程物理水凝胶

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摘要

Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol-gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from ≈9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.
机译：当前将细胞包封在物理水凝胶中的方案要求环境条件（pH，温度或离子强度）发生重大变化以引发凝胶化。这些状况可能对细胞有害，并且通常难以复制，因此使它们在临床环境中的使用变得复杂。我们报告了两成分的分子识别凝胶化战略的发展，该战略使细胞封装而无需环境触发。取而代之的是，包含WW和富含脯氨酸的肽结构域的多个重复的两个组分在肽结构域的简单混合和杂合后经历了溶胶-凝胶相转变。我们称这些材料为混合诱导的两组分水凝胶。我们的结果证明了在蛋白质工程材料中使用WW和富含脯氨酸的结构域，并将成功设计的肽库扩展为工程蛋白质。由于这两个缔合域通常都在细胞内发现，因此它们的分子识别不会被细胞外环境中其他生物分子的存在所破坏，从而可重现封装多种细胞类型，包括PC-12神经元样细胞，人脐静脉内皮细胞细胞和鼠类成体神经干细胞。两个组分的分子水平设计的精确变化，包括（i）每条链重复的缔合结构域的频率和（ii）域之间的缔合能，可定制水凝胶粘弹性以实现≈9至50的平稳剪切模量Pa。由于缔合域之间形成了短暂的物理交联，这些水凝胶具有剪切稀化，可注射和自修复的作用。封装在水凝胶中的神经干细胞形成稳定的三维培养物，该培养物继续自我更新，分化和发芽延伸的神经突。

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