Single-cell force spectroscopy

Helenius, Jonne; Heisenberg, Carl‐Philipp; Gaub, Hermann E.; Müller, Daniel J.

doi:10.1242/jcs.030999

Cited by 452 publications

(505 citation statements)

References 65 publications

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“…Since AFM-based assays make it possible to measure a wide range of forces applicable in cell studies (5 pN-100 nN), they are considered as useful tools for studying cell-cell or cell-surface interactions (Helenius et al 2008). AFM-based SCFS are also associated with a high precision, which allows spatial and temporal manipulation of cells during the experiment (Friedrichs et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Jalali

Tafazzoli-Shadpour

Haghighipour

et al. 2015

Cell Communication & Adhesion

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Although substrate stiffness has been previously reported to affect various cellular aspects, such as morphology, migration, viability, growth, and cytoskeletal structure, its influence on cell adherence has not been well examined. Here, we prepared three soft, medium, and hard polyacrylamide (PAAM) substrates and utilized AFM to study substrate elasticity and also the adhesion and mechanical properties of endothelial cells in response to changing substrate stiffness. Maximum detachment force and cell stiffness were increased with increasing substrate stiffness. Maximum detachment force values were 0.28 ± 0.14, 0.94 ± 0.27, and 1.99 ± 0.59 nN while Young's moduli of cells were 218. 85 ± 38.73, 385.58 ± 131.67, and 933.20 ± 428.92 Pa for soft, medium, and hard substrates, respectively. Human umbilical vein endothelial cells (HUVECs) showed round to more spread shapes on soft to hard substrates, with the most organized and elongated actin structure on the hard hydrogel. Our results confirm the importance of substrate stiffness in regulating cell mechanics and adhesion for a successful cell therapy. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Jalali

Tafazzoli-Shadpour

Haghighipour

et al. 2015

Cell Communication & Adhesion

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“…17 In order to better understand the role of focal adhesions in the rounding up of cells during mitosis, we investigated the adhesion of osteosarcoma cells to a glass substrate at different phases of the cell cycle ͑G 1 , S, and G 2 M͒ using atomic force microscopy ͑AFM͒. 18 AFM was originally developed for high-resolution imaging but it has also become a powerful tool to manipulate biomolecules 19,20 or cells 21,22 and to investigate forces in the piconewton range. 23,24 In AFM force spectroscopy, the cantilever is moved toward a sample or a surface until it is in contact with it and then retracted while the interaction forces between the cantilever and surface are measured.…”

Section: Introductionmentioning

confidence: 99%

Measuring cell adhesion forces during the cell cycle by force spectroscopy

Weder¹,

Vörös²,

Giazzon³

et al. 2009

Biointerphases

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Force spectroscopy has been used to measure the adhesion of Saos-2 cells to a glass surface at different phases of the cell cycle. The cells were synchronized in three phases of the cell cycle: G 1 , S, and G 2 M. Cells in these phases were compared with unsynchronized and native mitotic cells. Individual cells were attached to an atomic force microscope cantilever, brought into brief contact with the glass surface, and then pulled off again. The force-distance curves obtained allowed the work and maximum force of detachment as well as the number, amplitude, and position of discrete unbinding steps to be determined. A statistical analysis of the data showed that the number of binding proteins or protein complexes present at the cell surface and their binding properties remain similar throughout the cell cycle. This, despite the huge changes in cell morphology and adhesion that occur as the cells enter mitosis. These changes are rather associated with the changes in cytoskeletal organization, which can be quantified by force spectroscopy as changes in cell stiffness.

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“…Currently, the outcomes of AFM experiments are dependent on several factors, e.g., the quality of the sample and tip-preparation procedures, the quality of data recorded, and the accuracy of data interpretation [11], which are closely related to the experience of the operator. Especially for the experiments of molecular recognition, it requires the functionalization of the cantilever (e.g., linking molecule, virus, or cell to the cantilever [66,67]), which is labor-intensive and needs specific expertise. Hence, establishing simple standardized protocols for AFM experiments (including tip/ sample preparation, instrumental preparation, parameter calibration, data recording, data interpretation, and data analysis) will not only facilitate the newcomers to quickly grasp this technology but also will reduce the artificial effects.…”

Section: Discussionmentioning

confidence: 99%

Applications of Atomic Force Microscopy in Exploring Drug Actions in Lymphoma-Targeted Therapy at the Nanoscale

Liu

et al. 2015

BioNanoSci.

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Rituximab, a monoclonal antibody against the CD20 molecule expressed on B cells, has revolutionized the treatment of B cell lymphomas. The use of rituximab significantly improves the long-term survival rates of lymphoma patients. However, there are still many patients who develop resistance to rituximab. Hence, the urgent need is enhancing the potency of anti-CD20 antibodies beyond that achieved with rituximab to provide effective therapies for more patients. Traditional studies about the killing mechanisms of rituximab are commonly based on optical microscopy, which cannot reveal the detailed situations due to the limit of 200-nm resolution. Quantitatively investigating the actions of rituximab at the nanoscale is still scarce. The advent of atomic force microscopy (AFM) provides a powerful and versatile platform for in situ investigating the nanoscale behaviors of individual live cells. The applications of AFM in life sciences in the past decade have yielded a lot of novel insights into cell biology and related diseases. In this article, the typical applications (e.g., ultra-microstructures, mechanical properties, and molecular recognition) of AFM in investigating the three killing mechanisms of rituximab at the nanoscale are summarized; the challenges facing AFM single-cell assay and its future directions are also discussed.

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Single-cell force spectroscopy

Cited by 452 publications

References 65 publications

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

Measuring cell adhesion forces during the cell cycle by force spectroscopy

Applications of Atomic Force Microscopy in Exploring Drug Actions in Lymphoma-Targeted Therapy at the Nanoscale

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