Ripple scan

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The research from Washington University in St. Louis suggests that these other tissues could potentially be targeted to help treat cancer. Instead of competing with tumors for nutrients, other tissues can reprogram their metabolism to be complementary. Patti is the corresponding author of the study published May 13 in Cell Metabolism. Cancer consumes tremendous amounts of glucose, a key source of energy for cells in the body. Glucose, or blood sugar, is derived from food and transported around the body through the bloodstream after eating.

Tumors actively soak up glucose as a fuel to support their rapid growth. This trait is so well known that physicians regularly use it as a diagnostic test for cancer, where patients are administered a specific form of glucose that can be monitored with a PET scan. We wanted to know whether a tumor with a high avidity for glucose might influence glucose levels in the blood. Even when healthy people go a long period of time without eating, blood glucose levels are kept relatively constant.

That is because glucose can be made by the liver when it cannot be obtained directly from food. Gary Patti is an expert in the field of metabolomics , the comprehensive study of small molecules within a biological system. The scientists fed the zebrafish special versions of nutrients tagged with isotope labels.

These labels allowed the scientists to track where nutrients go and into what molecules they get broken down. They found that a molecule being spit out by the tumor was being taken up by the liver to make glucose. By applying metabolomics to individual zebrafish, the scientists observed that melanoma tissues in the body consume about 15 times more glucose than the other tissues they measured.

Despite this burden, the zebrafish were able to maintain circulating glucose levels, apparently by making glucose in the liver through a process that is ordinarily triggered when we go without eating. But it was clear that otherwise healthy tissues were affected in many ways by the presence of melanoma. The scientists examined tissues in the liver, intestine, fin, muscle, brain, blood, and eye of the zebrafish.

They observed metabolic dysregulation across most of the tissues — indicating that melanoma broadly impacts whole-body metabolism. BCAT1 goes from essentially being turned off in healthy skin cells to being highly expressed in zebrafish melanoma.

Both calculations of the stiffness and of the elastic modulus are based on the assumptions of the geometry of tip and sample. Since these are valid for the present measurement, it can be concluded that the sample topography does not affect the determination of these two quantities. This assumption is confirmed by the adhesion map in Figure 2D.

A larger contact area would yield a higher adhesion force [ Cappella, , p. On the contrary, the data show almost no variation of the adhesion force and no correlation at all with the topography. This proves that the above results for PnBMA are not affected by artefacts due to the topography and represent a valid analysis of its mechanical properties. Additionally, the profile of the tip grey is drawn in the graphs to show the proportions. Since, on PS, the gradient angle of the surface topography is almost as large as the opening angle of the tip, the phase shift between height and stiffness can be considered an artefact.

For PS, however, there is a phase shift between the height and stiffness data, as shown in Figure 3B. The maximum stiffness of 0. However, the phase shift between height and stiffness on PS is most probably an artefact, caused by the smaller wavelength of the ripples. For PS, the gradient angle of the surface topography approaches the opening angle of the tip. The narrower the ripples are, the more it becomes likely that the side of the tip touches the flank of the ripples when recording a force distance curve.

Therefore, because of the inclination angle and asymmetry of the tip, the contact area and the calculated stiffness are larger on the left side of the bundles compared to the right side. This is illustrated by drawing the tip both on the right side dark gray and on the left side light gray of a bundle in Figure 3B , which shows a larger contact on the left side.

Accordingly, the adhesion force measured on the left side is larger, as shown in Figure 2D. Because of the narrow ripples, a valid analysis of mechanical properties using Hertz theory is not possible on PS, other than on PnBMA. Therefore, the elastic modulus has not been calculated for PS. The measurements of mechanical properties and adhesion contribute to the understanding of the mechanisms leading to the formation of ripples. The lower stiffness and elastic modulus on the bundles imply a lower density of polymer chains in such agglomerations, which can be due both to loosening of polymer chains and to the presence of voids.

The stiffness and the elastic modulus in the troughs, however, are the same as on the unperturbed polymer film, which implies that the polymer density remains unchanged here. In this context, care must be taken to ensure that the ripple wavelength is large enough to exclude an effect of the topography on the calculation of the stiffness via the contact radius.

Otherwise, the data will be affected by an artefact, as observed for PS in the present study. In addition to the change in stiffness, the volume compared to the unperturbed film is increased by 0. Such a volume increase is in accordance with literature Iwata et al. These results strongly support the theory of crack propagation and the presence of voids in the bundles Elkaakour et al. Another method to characterize ripple structures is measuring the friction force. Similar to the force volume measurements shown in Figure 2 , the measurements were conducted on an area containing both ripples and unperturbed polymer surface.

The lateral signal is calculated as half the difference between the lateral trace and retrace signals. As the lateral signal depends on the friction force and on the topography gradient see Eq. It is clear that the lateral signal and the topography gradient angle do not correlate.

Therefore, the lateral signal is plotted against the topography signal as well, which is shown in Figure 4B. Here, a clear correlation between lateral and height signal can be seen. The lateral signal on the unperturbed polymer surface, shown by the dotted line in Figure 4B , is the same as the signal in the troughs. Hence, the friction is larger on the bundles, while, in the troughs, it remains the same as on the unperturbed polymer. Single profile lines of the lateral signal half difference between trace and retrace on PS ripples continuous red line and unperturbed film dotted red line , plotted together with A the gradient angle and B the height blue.

Therefore, cantilevers with a much smaller spring constant were used for friction experiments on PnBMA. The lateral signal, together with the topography gradient angle and the height signal, are shown in Figures 5A,B , respectively. The lateral signal does not correlate with the topography gradient angle, but unlike on PS, it does not correlate with the height signal either. The friction increases only at the left side of the bundles, while on the remaining parts of the ripple structure it remains the same as on the unperturbed polymer surface.

The lack of correlation is probably caused by the high compliance of the polymer, which leads to significant deformations and to changes of the contact area during the scanning. Additionally, the ripple structures on PnBMA are not as temporarily stable as they are on a glassy polymer. A decrease of their amplitude was observed in consecutive measurements. This shows that, at room temperature, PnBMA chains have enough energy to relax between the machining of the ripples and the friction measurement, thereby reducing a possible contrast in friction.

Single profile lines of the lateral signal half difference between trace and retrace on PnBMA ripples continuous red line and unperturbed film dotted red line , plotted together with A the gradient angle and B the height blue. The friction measurements support the interpretation of the force volume measurements. Like in Schmidt et al.

However, in the present study, a clear correlation between topography and stiffness was observed, which contrasts with Schmidt et al. The reason for this new result might be the larger amplitude and wavelength of the ripples, as well as the higher lateral measurement resolution in the present study. Just like the stiffness, the friction is changed only on the bundles, and remains unchanged in the troughs. The friction increase again implies that the bundles are aggregations of polymer chains, which are more lose than the original surface and filled with voids.

The structure of the polymers in the troughs, however, is not affected, but stays the same as in the unperturbed film. It is important to note that the present study also shows the limits of both force volume and friction measurements on polymer ripples. On such compliant, soft and small structures, those techniques are susceptible to artefacts, mainly due to deformation and changes of the contact area. While a force volume analysis requires ripples to be significantly wider than the tip, friction measurements yield meaningful contrasts only on a glassy polymer.

On the bundles, the modulus is reduced, and the friction is increased. In the latter case, our results support the theory of crack propagation as an underlying mechanism for the ripple formation. In the troughs, however, both modulus and friction remain unchanged compared to the unperturbed film. Therefore, it can be concluded that the polymer structure is changed only in the bundles. Two kinds of artefacts were observed in our experiments, and care must be taken to avoid them when using the described measurement methods.

Firstly, force volume measurements were proved to be a valuable method to quantitatively access mechanical properties of ripple structures. However, a reliable analysis using elastic continuum theories is only possible if the ripples are significantly wider than the tip, so that the sample can be always assumed as a plane indented by a hemisphere or a paraboloid and the contact area is not affected by the topography.

Secondly, the measurement of friction through the torsion of the cantilever only makes sense if the sample is not too compliant, i. Otherwise, the polymer is significantly deformed by scanning in contact mode, even with low forces. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. SF contributed to the conceptualization of the study, performed the experiments, contributed to the analysis and wrote the first draft of the article.

BC contributed to the conceptualization of the study and to the analysis and wrote sections of the article. All authors contributed to manuscript revision, read, and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Bonaccurso, E. B , — Butt, H. Cappella, B. Polymers , 3, — Berlin: Springer. Macromolecules 39, — Macromolecules 38, — Beilstein J. Dongmo, L. Ultramicroscopy , 85, — Elkaakour, Z. Gotsmann, B. Nano Lett. Hutter, J. Scientific Instr. Iwata, F. Nanotechnology 11, 10— Leach, R. Langmuir 19, — Leung, O. Science , 64— Meyers, G. Langmuir 8, — Munz, M. D: Appl. Napolitano, S. Nanotechnology 23, Ogletree, D. Schallamach, A. How Does Rubber Slide?

Wear 17, — Schmidt, R. Silbernagl, D. Scanning 32, — Sun, Y.

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