The study of the interactions of salts and osmolytes with macromolecules in aqueous solution originated with experiments concerning protein precipitation more than 100 years ago. Today, these solutes ...are known to display recurring behavior for myriad biological and chemical processes. Such behavior depends both on the nature and concentration of the species in solution. Despite the generality of these effects, our understanding of the molecular-level details of ion and osmolyte specificity is still quite limited. Here, we review recent studies of the interactions between anions and urea with model macromolecular systems. A mechanism for specific ion effects is elucidated for aqueous systems containing charged and uncharged polymers, polypeptides, and proteins. The results clearly show that the effects of the anions are local and involve direct interactions with macromolecules and their first hydration shell. Also, a hydrogen-bonding mechanism is tested for the urea denaturation of proteins with some of these same systems. In that case, direct hydrogen bonding can be largely discounted as the key mechanism for urea stabilization of uncollapsed and/or unfolded structures.
Anion effects on the cloud-point temperature for the liquid-liquid phase transition of lysozyme were investigated by temperature gradient microfluidics under a dark field microscope. It was found ...that protein aggregation in salt solutions followed 2 distinct Hofmeister series depending on salt concentration. Namely, under low salt conditions the association of anions with the positively charged lysozyme surface dominated the process and the phase transition temperature followed an inverse Hofmeister series. This inverse series could be directly correlated to the size and hydration thermodynamics of the anions. At higher salt concentrations, the liquid-liquid phase transition displayed a direct Hofmeister series that correlated with the polarizability of the anions. A simple model was derived to take both charge screening and surface tension effects into account at the protein/water interface. Fitting the thermodynamic data to this model equation demonstrated its validity in both the high and low salt regimes. These results suggest that in general positively charged macromolecular systems should show inverse Hofmeister behavior only at relatively low salt concentrations, but revert to a direct Hofmeister series as the salt concentration is increased.
Phase separation of intrinsically disordered proteins (IDPs) is a remarkable feature of living cells to dynamically control intracellular partitioning. Despite the numerous new IDPs that have been ...identified, progress towards rational engineering in cells has been limited. To address this limitation, we systematically scanned the sequence space of native IDPs and designed artificial IDPs (A-IDPs) with different molecular weights and aromatic content, which exhibit variable condensate saturation concentrations and temperature cloud points in vitro and in cells. We created A-IDP puncta using these simple principles, which are capable of sequestering an enzyme and whose catalytic efficiency can be manipulated by the molecular weight of the A-IDP. These results provide a robust engineered platform for creating puncta with new, phase-separation-mediated control of biological function in living cells.
The Hofmeister series, first noted in 1888, ranks the relative influence of ions on the physical behavior of a wide variety of aqueous processes ranging from colloidal assembly to protein folding. ...Originally, it was thought that an ion's influence on macromolecular properties was caused at least in part by ‘making’ or ‘breaking’ bulk water structure. Recent time-resolved and thermodynamic studies of water molecules in salt solutions, however, demonstrate that bulk water structure is not central to the Hofmeister effect. Instead, models are being developed that depend upon direct ion–macromolecule interactions as well as interactions with water molecules in the first hydration shell of the macromolecule.
Pericardial Effusions: Causes, Diagnosis, and Management Vakamudi, Sneha; Ho, Natalie; Cremer, Paul C
Progress in cardiovascular diseases,
2017, January-February 2017, 2017 Jan - Feb, 2017-01-00, Letnik:
59, Številka:
4
Journal Article
Recenzirano
Abstract The presentation of a patient with a pericardial effusion can range from an incidental finding to a life-threatening emergency. Accordingly, the causes of pericardial effusions are numerous ...and can generally be divided into inflammatory and non-inflammatory etiologies. For all patients with a suspected pericardial effusion, echocardiography is essential to define the location and size of an effusion. In pericardial tamponade, the hemodynamics relate to decreased pericardial compliance, ventricular interdependence, and an inspiratory decrease in the pressure gradient for left ventricular filling. Echocardiography provides insight into the pathophysiologic alterations, primarily through an assessment of chamber collapse, inferior vena cava plethora, and marked respiratory variation in mitral and tricuspid inflow. Once diagnosed, pericardiocentesis is performed in patients with tamponade, preferably with echocardiographic guidance. With a large effusion but no tamponade, pericardiocentesis is rarely needed for diagnostic purposes, though is performed if there is concern for a bacterial infection. In patients with malignancy, pericardial window is preferred given the risk for recurrence. Finally, large effusions can progress to tamponade, but can generally be followed closely until the extent of the effusion facilitates safe pericardiocentesis.
On planet Earth, water is everywhere: the majority of the surface is covered with it; it is a key component of all life; its vapour and droplets fill the lower atmosphere; and even rocks contain it ...and undergo geomorphological changes because of it. A community of physical scientists largely drives studies of the chemistry of water and aqueous solutions, with expertise in biochemistry, spectroscopy and computer modelling. More recently, however, supramolecular chemists - with their expertise in macrocyclic synthesis and measuring supramolecular interactions - have renewed their interest in water-mediated non-covalent interactions. These two groups offer complementary expertise that, if harnessed, offer to accelerate our understanding of aqueous supramolecular chemistry and water writ large. This Review summarizes the state-of-the-art of the two fields, and highlights where there is latent chemical space for collaborative exploration by the two groups.
The ability of cells or cell components to move in response to chemical signals is critical for the survival of living systems. This motion arises from harnessing free energy from enzymatic ...catalysis. Artificial model protocells derived from phospholipids and other amphiphiles have been made and their enzymatic-driven motion has been observed. However, control of directionality based on chemical cues (chemotaxis) has been difficult to achieve. Here we show both positive or negative chemotaxis of liposomal protocells. The protocells move autonomously by interacting with concentration gradients of either substrates or products in enzyme catalysis, or Hofmeister salts. We hypothesize that the propulsion mechanism is based on the interplay between enzyme-catalysis-induced positive chemotaxis and solute-phospholipid-based negative chemotaxis. Controlling the extent and direction of chemotaxis holds considerable potential for designing cell mimics and delivery vehicles that can reconfigure their motion in response to environmental conditions.
The interfacial water structure and phosphate group hydration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine monolayers were investigated at air/water interfaces. Both vibrational sum frequency ...spectroscopy (VSFS) and Langmuir monolayer compression measurements were made. The PC lipids oriented water molecules predominantly through their phosphate-choline (P-N) dipoles and carbonyl moieties. Upon the introduction of low concentrations of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), a positively charged double chain surfactant, the TAP headgroups were attracted to the phosphate moieties on adjacent PC lipids. This attraction caused the monolayers to contract, expelling water molecules that were hydrogen bonded to the phosphate groups. Moreover, amplitude of the OH stretch signal decreased. At higher DOTAP concentrations, the positive charge on the monolayer caused an increase in the area per headgroup and water molecules in the near-surface bulk region became increasingly aligned. Under these latter conditions, the OH stretch amplitude was linearly proportional to the surface potential. By contrast, introducing 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol, a negatively charged lipid, did not change the area per lipid or the phosphate–water hydrogen bonding network. As the interfacial potential grew more negative, the OH stretch amplitude increased continuously. Significantly, changes in the interfacial water spectrum were independent of the chemistry employed to create the positive or negative interfacial potential. For example, Ca2+ and tetracaine (both positively charged) disrupted the water structure similarly to low DOTAP concentrations, whereas SCN– and ibuprofen (both negatively charged) enhanced the water structure. These results suggest a direct correlation amongst the interfacial water structure, area per lipid, and surface charge density.
Ions differ in their ability to salt out proteins from solution as expressed in the lyotropic or Hofmeister series of cations and anions. Since its first formulation in 1888, this series has been ...invoked in a plethora of effects, going beyond the original salting out/salting in idea to include enzyme activities and the crystallization of proteins, as well as to processes not involving proteins like ion exchange, the surface tension of electrolytes, or bubble coalescence. Although it has been clear that the Hofmeister series is intimately connected to ion hydration in homogeneous and heterogeneous environments and to ion pairing, its molecular origin has not been fully understood. This situation could have been summarized as follows: Many chemists used the Hofmeister series as a mantra to put a label on ion-specific behavior in various environments, rather than to reach a molecular level understanding and, consequently, an ability to predict a particular effect of a given salt ion on proteins in solutions. In this Feature Article we show that the cationic and anionic Hofmeister series can now be rationalized primarily in terms of specific interactions of salt ions with the backbone and charged side chain groups at the protein surface in solution. At the same time, we demonstrate the limitations of separating Hofmeister effects into independent cationic and anionic contributions due to the electroneutrality condition, as well as specific ion pairing, leading to interactions of ions of opposite polarity. Finally, we outline the route beyond Hofmeister chemistry in the direction of understanding specific roles of ions in various biological functionalities, where generic Hofmeister-type interactions can be complemented or even overruled by particular steric arrangements in various ion binding sites.
PDF
