State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin 300071, China.
Physical Chemistry, Department of Chemistry, and Center for Integrated Protein Science Munich (CIPSM) and Nanosystems Initiative Munich (NIM), Ludwig-Maximilians-Universität, München 81377, Germany.
Nano Lett. 2021 Jan 13;21(1):642-650. doi: 10.1021/acs.nanolett.0c04216. Epub 2020 Dec 8.
Brain diseases are becoming a more and more serious threat to human health. Many critical properties of the transport mechanisms of drugs in live brains remain poorly understood. In this work, single-particle tracking was used to dissect the transport dynamics of wheat germ agglutinin (WGA) in live brain and characterize the geometry and rheology of the extracellular space (ECS). The results revealed that the movements of WGA were influenced by the specific-binding molecules and the nature of the ECS. We further analyzed the mobility behaviors of WGA globally and quantitatively and found that movement of WGA in brain cells of acute slices was an active transport process associated with actin filaments and microtubules. This work paves the way for studies aiming at characterizing the biophysics of drug transport in the context of live brains, which may contribute to developing potential new therapeutic applications for brain diseases.
脑部疾病正成为人类健康越来越严重的威胁。许多药物在活脑内运输机制的关键性质仍未被充分了解。在这项工作中，使用单颗粒跟踪技术来剖析小麦胚凝集素（WGA）在活脑内的运输动力学，并描述细胞外空间（ECS）的几何形状和流变特性。结果表明，WGA 的运动受到特异性结合分子和 ECS 性质的影响。我们进一步对 WGA 的整体和定量迁移行为进行了分析，发现 WGA 在急性脑片细胞内的运动是一种与肌动蛋白丝和微管相关的主动运输过程。这项工作为旨在研究活脑内药物运输的生物物理学特性的研究铺平了道路，这可能有助于为脑部疾病开发潜在的新治疗应用。
