MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics

High metastasis-associated in colon cancer 1 (MACC1) expression is associated with metastasis, tumor cell migration, and increased proliferation in colorectal cancer. Tumors with high MACC1 expression show a worse prognosis and higher invasion into neighboring structures. However, the mediation of the pro-migratory effects is still a matter of investigation.*

In their study “MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics”  Tim Hohmann, Urszula Hohmann, Mathias Dahlmann,  Dennis Kobelt, Ulrike Stein and Faramarz Dehghani aim to elucidate the impact of single cell biomechanics and proliferation on MACC1-dependent migration.*

The authors found that MACC1 expression associated with increased collective migration, caused by increased proliferation, and no changes in single cell biomechanics. Thus, targeting proliferation in high-MACC1-expressing tumors may offer additional effects on cell migration.*

The mechanical properties of single cells were assessed in the form of the Young’s modulus and cortex tension; both were measured using atomic force microscopy. Briefly, cells were seeded on a petri dish and measured 15 min after seeding to avoid slippage of individual cells. Measurements were conducted using a tipless NanoWorld Arrow-TL2 AFM cantilever array to apply a force of 1 nN that led to deformations of 1–2 µm. The Young’s modulus was calculated using the Hertz model.*

NanoWorld tipless Arrow-TL2 AFM probe array with two tipless AFM cantilevers
NanoWorld® Arrow™ TL2 AFM probes are tipless AFM cantilevers for special applications. They can for example be used for attaching spheres and other objects to the free end of the AFM cantilever, or for functionalizing and sensing applications.
The Arrow™ TL2 probes are optionally available with a sample facing side gold coating (Arrow™ TL2Au).
Figure 1 from “MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics” by Tim Hohmann et al. Single cell properties of high- and low-MACC1-expressing colon carcinoma cells. (A,B) depict the results of the biomechanical measurements for the Young´s modulus and the cortex tension. (C,D) show the results of live cell imaging of single cells for the mean speed and the contact area with the substrate. Sample sizes: (A) nSW480/EV = 35; nSW480/MACC1 = 33; nSW620/shMACC1 = 40; nSW620/shCTL = 40. (B) nSW480/EV = 33; nSW480/MACC1 = 31; nSW620/shMACC1 = 25; nSW620/shCTL = 26. (C,D) nSW480/EV = 66; nSW480/MACC1 = 98; nSW620/shMACC1 = 102; nSW620/shCTL = 111. Asterisk depicts statistically significant results with p < 0.05. Box plots show the median (red line), 25 and 75 percentile (box), non-outlier range (whiskers), and outliers (red dots). The mechanical properties of single cells were assessed in the form of the Young’s modulus and cortex tension; both were measured using atomic force microscopy. Briefly, cells were seeded on a petri dish and measured 15 min after seeding to avoid slippage of individual cells. Measurements were conducted using a NanoWorld Arrow-TL2 AFM cantilever to apply a force of 1 nN that led to deformations of 1–2 µm. The Young’s modulus was calculated using the Hertz model.
Figure 1 from “MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics” by Tim Hohmann et al.
Single cell properties of high- and low-MACC1-expressing colon carcinoma cells. (A,B) depict the results of the biomechanical measurements for the Young´s modulus and the cortex tension. (C,D) show the results of live cell imaging of single cells for the mean speed and the contact area with the substrate. Sample sizes: (A) nSW480/EV = 35; nSW480/MACC1 = 33; nSW620/shMACC1 = 40; nSW620/shCTL = 40. (B) nSW480/EV = 33; nSW480/MACC1 = 31; nSW620/shMACC1 = 25; nSW620/shCTL = 26. (C,D) nSW480/EV = 66; nSW480/MACC1 = 98; nSW620/shMACC1 = 102; nSW620/shCTL = 111. Asterisk depicts statistically significant results with p < 0.05. Box plots show the median (red line), 25 and 75 percentile (box), non-outlier range (whiskers), and outliers (red dots).

*Tim Hohmann, Urszula Hohmann, Mathias Dahlmann,  Dennis Kobelt, Ulrike Stein and Faramarz Dehghani
MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics
Cancers 2022, 14(12), 2857
DOI: https://doi.org/10.3390/cancers14122857

Open Access

The article “MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics” by Tim Hohmann, Urszula Hohmann, Mathias Dahlmann,  Dennis Kobelt, Ulrike Stein and Faramarz Dehghani is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy

Stem cell apoptosis exists widely in embryonic development, tissue regeneration, repair, aging and pathophysiology of disease. The molecular mechanism of stem cell apoptosis has been extensively investigated.*

However, alterations in biomechanics and nanomorphology have rarely been studied.*

In the research article “ Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy “ Xuelian Su, Haijing Zhou, Guangjie Bao, Jizeng Wang, Lin Liu, Qian Zheng, Manli Guo and Jinting Zhang establish an apoptosis model for bone marrow mesenchymal stem cells (BMSCs) and investigated in detail the reconstruction of the mechanical properties and nanomorphology of the cells.*

Atomic force microscopy (AFM), scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), flow cytometry and Cell Counting Kit-8 analysis were applied to assess the cellular elasticity modulus, geometry, nanomorphology, cell surface ultrastructure, biological viability and early apoptotic signals (phosphatidylserine,PS).*

The results indicated that the cellular elastic modulus and volume significantly decreased, whereas the cell surface roughness obviously increased during the first 3 h of cytochalasin B (CB) treatment. Moreover, these alterations preceded the exposure of biological apoptotic signal PS.*

These findings suggested that cellular mechanical damage is connected with the apoptosis of BMSCs, and the alterations in mechanics and nanomorphology may be a sensitive index to detect alterations in cell viability during apoptosis. The results contribute to further understanding of apoptosis from the perspective of cell mechanics.*

NanoWorld PNP Silicon Nitride AFM probes of the PNP-DB type were used for the single-cell imaging with Atomic Force Microscopy and nanoindentation experiments described in this research article.*

Figure 4 from “Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy” by Xuelian Su et al.:
Surface topography of BMSCs captured by AFM at different times. Columns A–D indicated the height-measurement images, vertical deflection images, three-dimensional images and cross-sectional images, respectively. The bright area was the elevated part of the cell, where the nucleus was located(A,C). The untreated cells adhered well, and their surface was smooth. The texture of the F-actin bundles is clearly visible (B, 0 h). The surface of treated cells became increasingly rough, the periphery of the cells became irregular and the area of cell extension gradually decreased (A and B, 1 h, 3 h, respectively).
Figure 4 from “Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy” by Xuelian Su et al.:
Surface topography of BMSCs captured by AFM at different times. Columns A–D indicated the height-measurement images, vertical deflection images, three-dimensional images and cross-sectional images, respectively. The bright area was the elevated part of the cell, where the nucleus was located(A,C). The untreated cells adhered well, and their surface was smooth. The texture of the F-actin bundles is clearly visible (B, 0 h). The surface of treated cells became increasingly rough, the periphery of the cells became irregular and the area of cell extension gradually decreased (A and B, 1 h, 3 h, respectively).

*Xuelian Su, Haijing Zhou, Guangjie Bao, Jizeng Wang, Lin Liu, Qian Zheng, Manli Guo and Jinting Zhang
Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy
Biology Open (2020) 9, bio048108.
DOI: 10.1242/bio.048108

Please follow this external link to read the full article: https://bio.biologists.org/content/biolopen/9/3/bio048108.full.pdf

Open Access The article “ Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy “ by Xuelian Su, Haijing Zhou, Guangjie Bao, Jizeng Wang, Lin Liu, Qian Zheng, Manli Guo and Jinting Zhang is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP

Quantifying the adaptive mechanical behavior of living cells is essential for the understanding of their inner working and function.*

In their article “Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP” Mark Skamrahl, Huw Colin‐York, Liliana Barbieri and Marco Fritzsche use a combination of atomic force microscopy and fluorescence recovery after photobleaching is introduced which offers simultaneous quantification and direct correlation of molecule kinetics and mechanics in living cells.*

Simultaneous quantification of the relationship between molecule kinetics and cell mechanics may thus open up unprecedented insights into adaptive mechanobiological mechanisms of cells.*

For the AFM nanoindentation tests described in their publication the authors used NanoWorld Arrow-TL2 tipless cantilevers that were functionalized with a polystyrene bead with 5 µm radius.*

 Figure 1 a from “Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP” by M. Skamrahl et al.: 
 Establishment and calibration of the optomechanical AFM–FRAP platform. a) Schematic of the AFM–FRAP setup illustrating the experimental power of simultaneous quantification of molecule kinetics and cell mechanics
Figure 1 a from “Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP” by M. Skamrahl et al.:
Establishment and calibration of the optomechanical AFM–FRAP platform. a) Schematic of the AFM–FRAP setup illustrating the experimental power of simultaneous quantification of molecule kinetics and cell mechanics

*Mark Skamrahl, Huw Colin‐York, Liliana Barbieri, Marco Fritzsche
Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP
Small 2019, 1902202
DOI: https://doi.org/10.1002/smll.201902202

Please follow this external link to the full article https://onlinelibrary.wiley.com/doi/full/10.1002/smll.201902202

Open Access: The article « Simultaneous Quantification of the Interplay Between Molecular Turnover and Cell Mechanics by AFM–FRAP » by Mark Skamrahl, Huw Colin‐York, Liliana Barbieri and Marco Fritzsche is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other thirdparty material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.