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Cellular systems must deal with mechanical forces to satisfy their physiological functions. In this context, proteins with mechanosensitive properties play a crucial role in sensing and responding to environmental changes. The discovery of aquaporins (AQPs) marked a significant breakthrough in the study of water transport. Their transport capacity and regulation features make them key players in cellular processes. To date, few AQPs have been reported to be mechanosensitive. Like mechanosensitive ion channels, AQPs respond to tension changes in the same range. However, unlike ion channels, the aquaporin's transport rate decreases as tension increases, and the molecular features of the mechanism are unknown. Nevertheless, some clues from mechanosensitive ion channels shed light on the AQP-membrane interaction. The GxxxG motif may play a critical role in the water permeation process associated with structural features in AQPs. Consequently, a possible gating mechanism triggered by membrane tension changes would involve a conformational change in the cytoplasmic extreme of the single file region of the water pathway, where glycine and histidine residues from loop B play a key role. In view of their transport capacity and their involvement in relevant processes related to mechanical forces, mechanosensitive AQPs are a fundamental piece of the puzzle for understanding cellular responses.

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Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.

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Aquaporins (AQPs) function as tetrameric structures in which each monomer has its own permeable pathway. The combination of structural biology, molecular dynamics simulations, and experimental approaches has contributed to improve our knowledge of how protein conformational changes can challenge its transport capacity, rapidly altering the membrane permeability. This review is focused on evidence that highlights the functional relationship between the monomers and the tetramer. In this sense, we address AQP permeation capacity as well as regulatory mechanisms that affect the monomer, the tetramer, or tetramers combined in complex structures. We therefore explore: (i) water permeation and recent evidence on ion permeation, including the permeation pathway controversy-each monomer versus the central pore of the tetramer-and (ii) regulatory mechanisms that cannot be attributed to independent monomers. In particular, we discuss channel gating and AQPs that sense membrane tension. For the latter we propose a possible mechanism that includes the monomer (slight changes of pore shape, the number of possible H-bonds between water molecules and pore-lining residues) and the tetramer (interactions among monomers and a positive cooperative effect).

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Aquaporins (AQPs) can be revisited from a distinct and complementary perspective: the outcome from analyzing them from both plant and animal studies. (1) The approach in the study. Diversity found in both kingdoms contrasts with the limited number of crystal structures determined within each group. While the structure of almost half of mammal AQPs was resolved, only a few were resolved in plants. Strikingly, the animal structures resolved are mainly derived from the AQP2-lineage, due to their important roles in water homeostasis regulation in humans. The difference could be attributed to the approach: relevance in animal research is emphasized on pathology and in consequence drug screening that can lead to potential inhibitors, enhancers and/or regulators. By contrast, studies on plants have been mainly focused on the physiological role that AQPs play in growth, development and stress tolerance. (2) The transport capacity. Besides the well-described AQPs with high water transport capacity, large amount of evidence confirms that certain plant AQPs can carry a large list of small solutes. So far, animal AQP list is more restricted. In both kingdoms, there is a great amount of evidence on gas transport, although there is still an unsolved controversy around gas translocation as well as the role of the central pore of the tetramer. (3) More roles than expected. We found it remarkable that the view of AQPs as specific channels has evolved first toward simple transporters to molecules that can experience conformational changes triggered by biochemical and/or mechanical signals, turning them also into signaling components and/or behave as osmosensor molecules.

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Previous works proposed that aquaporins behave as mechanosensitive channels. However, principal issues about mechanosensitivity of aquaporins are not known. In this work, we characterized the mechanosensitive properties of the water channels BvTIP1;2 (TIP1) and BvPIP2;1 (PIP2) from red beet (Beta vulgaris). We simultaneously measured the mechanical behavior and the water transport rates during the osmotic response of emptied-out oocytes expressing TIP1 or PIP2. Our results indicate that TIP1 is a mechanosensitive aquaporin, whereas PIP2 is not. We found that a single exponential function between the osmotic permeability coefficient and the volumetric elastic modulus governs the mechanosensitivity of TIP1. Finally, homology modeling analysis indicates that putative residues involved in mechanosensitivity show different quantity and distribution in TIP1 and PIP2.

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Plant cell vacuoles occupy up to 90% of the cell volume and, beyond their physiological function, are constantly subjected to water and solute exchange. The osmotic flow and vacuole volume dynamics relies on the vacuole membrane -the tonoplast- and its capacity to regulate its permeability to both water and solutes. The osmotic permeability coefficient (Pf ) is the parameter that better characterizes the water transport when submitted to an osmotic gradient. Usually, Pf determinations are made in vitro from the initial rate of volume change, when a fast (almost instantaneous) osmolality change occurs. When aquaporins are present, it is accepted that initial volume changes are only due to water movements. However, in living cells osmotic changes are not necessarily abrupt but gradually imposed. Under these conditions, water flux might not be the only relevant driving force shaping the vacuole volume response. In this study, we quantitatively investigated volume dynamics of isolated Beta vulgaris root vacuoles under progressively applied osmotic gradients at different pH, a condition that modifies the tonoplast Pf . We followed the vacuole volume changes while simultaneously determining the external osmolality time-courses and analyzing these data with mathematical modeling. Our findings indicate that vacuole volume changes, under progressively applied osmotic gradients, would not depend on the membrane elastic properties, nor on the non-osmotic volume of the vacuole, but on water and solute fluxes across the tonoplast. We found that the volume of the vacuole at the steady state is determined by the ratio of water to solute permeabilites (Pf /Ps ), which in turn is ruled by pH. The dependence of the permeability ratio on pH can be interpreted in terms of the degree of aquaporin inhibition and the consequently solute transport modulation. This is relevant in many plant organs such as root, leaves, cotyledons, or stems that perform extensive rhythmic growth movements, which very likely involve considerable cell volume changes within seconds to hours.

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This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.

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Present knowledge obtained by molecular dynamics (MD) simulation studies regarding the dynamics of water, both in the vicinity of biological membranes and within the proteinaceous water channels, also known as aquaporins (AQPs), is reviewed. A brief general summary of the water models most extensively employed in MD simulations (SPC, SPC/E, TIP3P, TIP4P), indicating their most relevant pros and cons, is likewise provided. Structural considerations of water are also discussed, based on different order parameters, which can be extracted from MD simulations as well as from experiments. Secondly, the behaviour of water in the neighbourhood of membranes by means of molecular dynamics simulations is addressed. Consequently, the comparison with previous experimental evidence is pointed out. In living cells, water is transported across the plasma membrane through the lipid bilayer and the aforementioned AQPs, which motivates this review to focus mostly on MD simulation studies of water within AQPs. Relevant contributions explaining peculiar properties of these channels are discussed, such as selectivity and gating. Water models used in these studies are also summarised. Finally, based on the information presented here, further MD studies are encouraged.

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OBJECTIVE: To evaluate the mechanisms of microbial interaction between the oral pathogens Candida albicans and Streptococcus mutans. MATERIALS AND METHODS: Growth kinetics for the two micro-organisms, cultured individually or together, were followed experimentally for 36 h. The different growth curves were analysed by means of mathematical modelling. RESULTS: Under the experimental conditions, S. mutans final concentration, when grown individually, was 5-times that of C. albicans. Contrarily, when both micro-organisms grew together, this ratio was inversed and C. albicans final concentration was even higher than that of S. mutans. When both micro-organisms share the niche, a model including linear competition among one another was best suited to reproduce the experimental observations. The results of this model show that the initial growth rates of both species are positively influenced by their mutual interaction. However, at longer incubation times, C. albicans prevents bacterial growth and achieves concentrations 4-times higher than when grown individually. CONCLUSIONS: The results suggest that C. albicans biofilm formation could be potentiated by the presence of S. mutans by two mechanisms: synergically at short times and by competition at longer periods.

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When new members join a working group dedicated to scientific research, several changes occur in the group's dynamics. From a teaching point of view, a subsequent challenge is to develop innovative strategies to train new staff members in creative thinking, which is the most complex and abstract skill in the cognitive domain according to Bloom's revised taxonomy. In this sense, current technological and digital advances offer new possibilities in the field of education. Computer simulation and biological experiments can be used together as a combined tool for teaching and learning sometimes complex physiological and biophysical concepts. Moreover, creativity can be thought of as a social process that relies on interactions among staff members. In this regard, the acquisition of cognitive abilities coexists with the attainment of other skills from psychomotor and affective domains. Such dynamism in teaching and learning stimulates teamwork and encourages the integration of members of the working group. A practical example, based on the teaching of biophysical subjects such as osmosis, solute transport, and membrane permeability, which are crucial in understanding the physiological concept of homeostasis, is presented.

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