Advances in cellular nanoscale force detection and manipulationby Shuchen Hsieh, I-Tin Li, Chiung-Wen Hsieh, Mei-Lang Kung, Shu-Ling Hsieh, Deng-Chyang Wu, Chao-Hung Kuo, Ming-Hong Tai, Huay-Min Wang, Wen-Jeng Wu, Bi-Wen Yeh

Arabian Journal of Chemistry

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Year
2015
DOI
10.1016/j.arabjc.2015.08.011
Subject
Chemistry (all) / Chemical Engineering (all)

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Accepted Manuscript

Advances in cellular nanoscale force detection and manipulation

Shuchen Hsieh, I-Tin Li, Chiung-Wen Hsieh, Mei-Lang Kung, Shu-Ling Hsieh,

Deng-Chyang Wu, Chao-Hung Kuo, Ming-Hong Tai, Huay-Min Wang, WenJeng Wu, Bi-Wen Yeh

PII: S1878-5352(15)00251-8

DOI: http://dx.doi.org/10.1016/j.arabjc.2015.08.011

Reference: ARABJC 1744

To appear in: Arabian Journal of Chemistry

Received Date: 16 December 2013

Accepted Date: 8 August 2015

Please cite this article as: S. Hsieh, I-T. Li, C-W. Hsieh, M-L. Kung, S-L. Hsieh, D-C. Wu, C-H. Kuo, M-H. Tai,

H-M. Wang, W-J. Wu, B-W. Yeh, Advances in cellular nanoscale force detection and manipulation, Arabian Journal of Chemistry (2015), doi: http://dx.doi.org/10.1016/j.arabjc.2015.08.011

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Advances in cellular nanoscale force detection and manipulation

Shuchen Hsieha,b,*, I-Tin Lia, Chiung-Wen Hsieha, Mei-Lang Kunga, Shu-Ling

Hsiehc, Deng-Chyang Wud,e, Chao-Hung Kuod,e, Ming-Hong Taif, Huay-Min Wangg,

Wen-Jeng Wuh,i,j,k and Bi-Wen Yehh,i aDepartment of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-sen

University, 70 Lien-Hai Rd, Kaohsiung 80424, Taiwan bSchool of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan cDepartment of Seafood Science, National Kaohsiung Marine University, Kaohsiung 81157, Taiwan dDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University

Hospital, Kaohsiung 80708, Taiwan eDepartment of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708,

Taiwan fInstitute of Biomedical Sciences, National Sun Yat-Sen University, 70, Lienhai Rd., Kaohsiung, 80424,

Taiwan gDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General

Hospital, 386 Ta-Chung 1st Road, Kaohsiung 81362, Taiwan h

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University,

Kaohsiung, Taiwan iDepartment of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University,

Kaohsiung, Taiwan jGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan kDepartment of Urology, Kaohsiung Municipal Hsiao-Kang Hospital,Kaohsiung Medical University,

Kaohsiung 80708, Taiwan *Corresponding author:

Shuchen Hsieh, Tel: +886 7 525 2000 ext 3931; Fax: +886 7 525 3908; E-mail address: shsieh@faculty.nsysu.edu.tw 2

Advances in cellular nanoscale force detection and manipulation

Shuchen Hsieha,b,*, I-Tin Lia, Chiung-Wen Hsieha, Mei-Lang Kunga, Shu-Ling

Hsiehc, Deng-Chyang Wud,e, Chao-Hung Kuod,e, Ming-Hong Taif, Huay-Min Wangg,

Wen-Jeng Wuh,i,j,k and Bi-Wen Yehh,i aDepartment of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-sen

University, 70 Lien-Hai Rd, Kaohsiung 80424, Taiwan bSchool of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan cDepartment of Seafood Science, National Kaohsiung Marine University, Kaohsiung 81157, Taiwan dDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University

Hospital, Kaohsiung 80708, Taiwan eDepartment of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708,

Taiwan fInstitute of Biomedical Sciences, National Sun Yat-Sen University, 70, Lienhai Rd., Kaohsiung, 80424,

Taiwan gDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General

Hospital, 386 Ta-Chung 1st Road, Kaohsiung 81362, Taiwan h

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University,

Kaohsiung, Taiwan iDepartment of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University,

Kaohsiung, Taiwan jGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan kDepartment of Urology, Kaohsiung Municipal Hsiao-Kang Hospital,Kaohsiung Medical University,

Kaohsiung 80708, Taiwan 3 *Corresponding author:

Shuchen Hsieh, Tel: +886 7 525 2000 ext 3931; Fax: +886 7 525 3908; E-mail address: shsieh@faculty.nsysu.edu.tw 4

Abstract

Biology and cellular mechanics have benefited from recent technological advances in physics and materials science, allowing researchers to make quantitative nanoscale force measurements to explore aspects of biological systems that were previously inaccessible. Atomic force microscopy (AFM) can be used to acquire high-resolution topographical images of cell surfaces in vivo and possesses the ability to detect the local mechanical properties of single cells on the nanometer scale. Interactions between the tip and sample cause the cantilever to deflect, which is measured using an optical lever system composed of a laser, cantilever, and photodiode. Deflections on the order of tens of picometers can be detected, which corresponds to forces of less than 10 pN when using an appropriate cantilever. Highly sensitive force detection with AFM has been used to measure differences in the surface brush of normal and cancerous cells and to determine the mechanical hardness of cellular cytoskeletal structures. The AFM probe has further been employed to perform surgical operations on cells, which enabled the injection of plasmid DNA into a living cell to modulate gene expression. The application of AFM for nanoscale force control and unique cellular surgery provides new methods for investigating cell properties for therapeutic purposes.

Keywords: AFM; Mechanical property; Force curve; Extracellular matrix; Matrix stiffness 5

Contents 1. Introduction 4 2. Experimental 6 2.1 Surface characterization 6 2.2 Force-distance curves and analysis of adhesion force 6 2.3 Statistical analysis of AFM force curves 8 2.4 Cell culture and sample prepare 9 3. Results and discussion 10 3.1 Ultra-sensitive detection of cellular mechanics 10 3.2 Molecular mechanical measurements by AFM 11 3.3 AFM-based cell adhesion interaction 13 3.3.1 Chemically functionalized probes for specific detection 16 3.3.2 Cellular level manipulation and treatment with AFM 17 4. Conclusion 19