关键词: cross-linking protein cage single-molecule force spectroscopy stabilization virus-like particles (VLPs)

Mesh : Capsid Proteins / chemistry Capsid / chemistry Maleimides / analysis

来  源:   DOI:10.1021/acs.nanolett.3c03806

Abstract:
Many virus-like particles (VLPs) have good chemical, thermal, and mechanical stabilities compared to those of other biologics. However, their stability needs to be improved for the commercialization and use in translation of VLP-based materials. We developed an endoskeleton-armored strategy for enhancing VLP stability. Specifically, the VLPs of physalis mottle virus (PhMV) and Qβ were used to demonstrate this concept. We built an internal polymer \"backbone\" using a maleimide-PEG15-maleimide cross-linker to covalently interlink viral coat proteins inside the capsid cavity, while the native VLPs are held together by only noncovalent bonding between subunits. Endoskeleton-armored VLPs exhibited significantly improved thermal stability (95 °C for 15 min), increased resistance to denaturants (i.e., surfactants, pHs, chemical denaturants, and organic solvents), and enhanced mechanical performance. Single-molecule force spectroscopy demonstrated a 6-fold increase in rupture distance and a 1.9-fold increase in rupture force of endoskeleton-armored PhMV. Overall, this endoskeleton-armored strategy provides more opportunities for the development and applications of materials.
摘要:
许多病毒样颗粒(VLP)具有良好的化学性质,热,与其他生物制品相比,机械稳定性。然而,它们的稳定性需要提高,以实现VLP材料的商业化和翻译。我们开发了一种内骨骼装甲策略来增强VLP的稳定性。具体来说,使用酸浆斑驳病毒(PhMV)和Qβ的VLP来证明这一概念。我们使用马来酰亚胺-PEG15-马来酰亚胺交联剂构建了内部聚合物“骨架”,以共价互连衣壳腔内的病毒外壳蛋白,而天然VLP仅通过亚基之间的非共价键结合在一起。内骨骼铠装的VLP表现出显着改善的热稳定性(95°C持续15分钟),对变性剂的抗性增加(即,表面活性剂,pH值,化学变性剂,和有机溶剂),和增强的机械性能。单分子力谱显示,内骨骼装甲的PhMV的破裂距离增加了6倍,破裂力增加了1.9倍。总的来说,这种内骨骼装甲策略为材料的开发和应用提供了更多机会。
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