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| 2. |
- Pham, Dat, et al.
(författare)
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Effects of Urea and TMAO on Lipid Self-Assembly under Osmotic Stress Conditions
- 2018
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 122:25, s. 6471-6482
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Tidskriftsartikel (refereegranskat)abstract
- Most land-living organisms regularly experience dehydration. In nature, one commonly applied strategy to protect against this osmotic stress is to introduce small polar molecules with low vapor pressure, commonly called osmolytes. Two examples of naturally occurring small polar compounds are urea and trimethylamine N-oxide (TMAO), which are known to have counteracting effects on protein stability. In this work, we investigate the effects of urea and TMAO on lipid self-assembly at varying water contents, focusing on dehydrated conditions. By using complementary experimental techniques, including sorption microcalorimetry, NMR, and X-ray scattering, together with molecular dynamics simulations in model systems composed of phosphatidylcholine lipids, water, and solute, we characterize interactions and self-assembly over a large range of hydration conditions. It is shown that urea and TMAO show qualitatively similar effects on lipid self-assembly at high water contents, whereas they have clearly different effects in dehydrated conditions. The latter can be explained by differences in the molecular interactions between the solutes and the lipid headgroups. TMAO is repelled from the bilayer interface, and it is thereby expelled from lipid lamellar systems with low water contents and narrow inter-bilayer regions. In these conditions, TMAO shows no effect on the lipid phase behavior. Urea, on the other hand, shows a slight affinity for the lipid headgroup layer, and it is present in the lipid lamellar system at all water contents. As a result, urea may exchange with water in dry conditions and thereby prevent dehydration-induced phase transitions. In nature, urea and TMAO are sometimes found together in the same organisms and it is possible that their combined effect is to both protect lipid membranes against dehydration and still avoid denaturation of proteins.
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| 3. |
- Reuten, Raphael, et al.
(författare)
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Basement membrane stiffness determines metastases formation
- 2021
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Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-4660 .- 1476-1122.
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Tidskriftsartikel (refereegranskat)abstract
- The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores. Our results therefore reveal that BM stiffness is dominant over pore size, and that the mechanical properties of ‘normal’ BMs determine metastases formation and patient survival independent of cancer-mediated alterations. Thus, identifying individual Net4 protein levels within native BMs in major metastatic organs may have the potential to define patient survival even before tumour formation. The ratio of Net4 to laminin molecules determines BM stiffness, such that the more Net4, the softer the BM, thereby decreasing cancer cell invasion activity.
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| 4. |
- Vrbka, Lubos, et al.
(författare)
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Ion-specific thermodynamics of multicomponent electrolytes: A hybrid HNC/MD approach
- 2009
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 131:15
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Tidskriftsartikel (refereegranskat)abstract
- Using effective infinite dilution ion-ion interaction potentials derived from explicit-water molecular dynamics (MD) computer simulations in the hypernetted-chain (HNC) integral equation theory we calculate the liquid structure and thermodynamic properties, namely, the activity and osmotic coefficients of various multicomponent aqueous electrolyte mixtures. The electrolyte structure expressed by the ion-ion radial distribution functions is for most ions in excellent agreement with MD and implicit solvent Monte Carlo (MC) simulation results. Calculated thermodynamic properties are also represented consistently among these three methods. Our versatile HNC/MD hybrid method allows for a quick prediction of the thermodynamics of multicomponent electrolyte solutions for a wide range of concentrations and an efficient assessment of the validity of the employed MD force-fields with possible implications in the development of thermodynamically consistent parameter sets. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3248218]
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| 5. |
- Wolde-Kidan, Amanuel, et al.
(författare)
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Influence of polar co-solutes and salt on the hydration of lipid membranes
- 2019
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 21:31, s. 16989-17000
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the co-solutes TMAO, urea, and NaCl on the hydration repulsion between lipid membranes is investigated in a combined experimental/simulation approach. Pressure-hydration curves obtained via sorption experiments reveal that the repulsion significantly increases when the membranes are loaded with co-solutes, most strongly for TMAO. As a result, the co-solutes retain additional water molecules and therefore provide membranes with a fluid and more physiological environment. The experimental data are quantitatively reproduced in complementary solvent-explicit atomistic molecular dynamics simulations, which yield the chemical potential of water. Simulation analysis reveals that the additional repulsion arises from the osmotic pressure generated by the co-solutes, an effect which is maximal for TMAO, due to its unfavorable interactions with the lipid headgroup layer and its extraordinarily high osmotic coefficient.
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