journal article·2023-03-28

Nanomechanical Profiling of Aβ42 Oligomer-Induced Biological Changes in Single Hippocampus Neurons

Dandan Li, Jiang Li, Jiao Hu, Mingjie Tang, Peng Xiu, Yunchang Guo, Tunan Chen, Ning Mu, Lihua Wang, Xuehua Zhang, Guizhao Liang, Huabin Wang, Chunhai Fan

ACS Nano· Volume 17· Issue 6
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Abstract

Understanding how Aβ42 oligomers induce changes in neurons from a mechanobiological perspective has important implications in neuronal dysfunction relevant to neurodegenerative diseases. However, it remains challenging to profile the mechanical responses of neurons and correlate the mechanical signatures to the biological properties of neurons given the structural complexity of cells. Here, we quantitatively investigate the nanomechanical properties of primary hippocampus neurons upon exposure to Aβ42 oligomers at the single neuron level by using atomic force microscopy (AFM). We develop a method termed heterogeneity-load-unload nanomechanics (HLUN), which exploits the AFM force spectra in the whole loading-unloading cycle, allowing comprehensive profiling of the mechanical properties of living neurons. We extract four key nanomechanical parameters, including the apparent Young's modulus, cell spring constant, normalized hysteresis, and adhesion work, that serve as the nanomechanical signatures of neurons treated with Aβ42 oligomers. These parameters are well-correlated with neuronal height increase, cortical actin filament strengthening, and calcium concentration elevation. Thus, we establish an HLUN method-based AFM nanomechanical analysis tool for single neuron study and build an effective correlation between the nanomechanical profile of the single neurons and the biological effects triggered by Aβ42 oligomers. Our finding provides useful information on the dysfunction of neurons from the mechanobiological perspective.
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Research context

OpenAlex topics: Cellular Mechanics and Interactions · Force Microscopy Techniques and Applications · Axon Guidance and Neuronal Signaling

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing University, Chongqing 400044, China

Center of Super-resolution Optics and Chongqing Engineering Research Center of High-Resolution and Three-Dimensional Dynamic Imaging Technology, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China

Chongqing School, University of Chinese Academy of Sciences, Chongqing 400714, China

Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China

Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China

Yihuang (Wuxi) Spectrum Measurement & Control Co., Ltd., Wuxi 214024, Jiangsu, China

Department of Neurosurgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China

Department of Chemical & Materials Engineering, University of Alberta, Edmonton T6G1H9, Alberta, Canada

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200024, China

Funding

University of Chinese Academy of Sciences · National Natural Science Foundation of China · National Key Research and Development Program of China

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