Kapon Yael, Merhav Dror, Finkelstein-Zuta Gal, Blumen Omer, Melamed-Book Naomi, Levi-Kalisman Yael, Torchinsky Ilya, Yochelis Shira, Sharon Daniel, Baczewski Lech Tomasz, Gazit Ehud, Paltiel Yossi
Institute of Applied Physics, The Hebrew University, Jerusalem 9190401, Israel.
The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
ACS Nano. 2025 Aug 12;19(31):28326-28334. doi: 10.1021/acsnano.5c06285. Epub 2025 Jul 28.
Protein aggregation into amyloid fibrils is central to numerous diseases, yet the role of electron spin interactions during nucleation and self-assembly remains unexplored. We investigated amyloid formation of A-β(1-42) polypeptide, implicated in Alzheimer's disease, and its smaller recognition motifs on ferromagnetic substrates. We observed a strong dependence of fibril formation dynamics on the substrate's magnetization orientation using electron and fluorescence microscopy. Specifically, one magnetization orientation yielded approximately twice as many and significantly longer (up to 20-fold) fibrils compared with the opposite orientation, a preference that flipped with the opposite monomer chirality. Furthermore, ATR-FTIR detected structural variations in the fibril structure, depending on the substrate magnetization. These findings suggest that transient spin polarization of the monomers during self-assembly, potentially driven by the Chiral-Induced Spin Selectivity (CISS) effect, plays a critical role in amyloid assembly dynamics. The consistency of these effects across different molecule length scales suggests a fundamental spin-based influence on biomolecular aggregation. This insight may have implications for therapeutic strategies, including the use of spin-polarized magnetic nanoparticles to selectively modulate amyloid formation in neurodegenerative diseases and the integration of spin-selective interfaces in dialysis systems to mitigate dialysis-related amyloidosis.
蛋白质聚集成淀粉样纤维是众多疾病的核心问题，然而在成核和自组装过程中电子自旋相互作用的作用仍未得到探索。我们研究了与阿尔茨海默病相关的A-β(1-42)多肽及其在铁磁基底上较小的识别基序的淀粉样形成。我们使用电子显微镜和荧光显微镜观察到纤维形成动力学对基底磁化方向有强烈依赖性。具体而言，一种磁化方向产生的纤维数量大约是相反方向的两倍，且明显更长（长达20倍），这种偏好会随着单体手性相反而翻转。此外，衰减全反射傅里叶变换红外光谱（ATR-FTIR）检测到纤维结构的结构变化，这取决于基底磁化情况。这些发现表明，在自组装过程中单体的瞬态自旋极化可能由手性诱导自旋选择性（CISS）效应驱动，在淀粉样组装动力学中起关键作用。这些效应在不同分子长度尺度上的一致性表明了基于自旋的对生物分子聚集的基本影响。这一见解可能对治疗策略有影响，包括使用自旋极化磁性纳米颗粒来选择性调节神经退行性疾病中的淀粉样形成，以及在透析系统中整合自旋选择性界面以减轻透析相关淀粉样变性。
