journal article·2022-03-22

Spatiotemporal Tracing of the Cellular Internalization Process of Rod-Shaped Nanostructures

Yi-Feng Wang, Qingrong Zhang, Falin Tian, Hongda Wang, Yufei Wang, Xiaowei Ma, Qianqian Huang, Mingjun Cai, Yinglu Ji, Xiaochun Wu, Yaling Gan, Yan Yan, Kenneth A. Dawson, Shutao Guo, Jinchao Zhang, Xinghua Shi, Yuping Shan, Xing-Jie Liang

ACS Nano· Volume 16· Issue 3
Publisher page

Abstract

Endocytosis, as one of the main ways for nanostructures enter cells, is affected by several aspects, and shape is an especially critical aspect during the endocytosis of nanostructures. However, it has remained challenging to capture the dynamic internalization behaviors of rod-shaped nanostructures while also probing the mechanical aspects of the internalization. Here, using the atomic force microscopy-based force tracing technique, transmission electron microscopy, and molecular dynamic simulation, we mapped the detailed internalization behaviors of rod-shaped nanostructures with different aspect ratios at the single-particle level. We found that the gold nanorod is endocytosed in a noncontinuous and force-rebound rotation manner, herein named "intermittent rotation". The force tracing test indicated that the internalization force (∼81 pN, ∼108 pN, and ∼157 pN) and time (∼0.56 s, ∼0.66 s, and ∼1.14 s for a 12.10 nm × 11.96 nm gold nanosphere and 26.15 nm × 13.05 nm and 48.71 nm × 12.45 nm gold nanorods, respectively) are positively correlated with the aspect ratios. However, internalization speed is negatively correlated with internalization time, irrespective of the aspect ratio. Further, the energy analysis suggested that intermittent rotation from the horizontal to vertical direction can reduce energy dissipation during the internalization process. Thus, to overcome the energy barrier of internalization, the number and angle of rotation increases with aspect ratios. Our findings provide critical missing evidence of rod-shaped nanostructure's internalization, which is essential for fundamentally understanding the internalization mechanism in living cells.
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Research context

OpenAlex topics: Force Microscopy Techniques and Applications · Nanoparticle-Based Drug Delivery · Lipid Membrane Structure and Behavior

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

Affiliations

Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China

University of Chinese Academy of Sciences, Beijing 100049, P.R. China

School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, P.R. China

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P.R. China

Laboratory of Theoretical and Computational Nanoscience, CAS Key Laboratory for Nanosystem and Hierarchy Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China

Centre for BioNano Interactions, School of Chemistry, School of Biomolecular and Biomedical Science, University College Dublin, Dublin D04 V1W8, Ireland

Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, P.R. China

Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P.R. China

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, P.R China

Funding

Natural Science Foundation of Hebei Province · Ministry of Science and Technology of the People's Republic of China · Natural Science Foundation of Beijing Municipality · China Postdoctoral Science Foundation · Chinese Academy of Sciences · Ten Thousand Elite Plan · National Natural Science Foundation of China · Beijing-Tianjin-Hebei Basic Research Cooperation Project

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