Stimuli-responsive membranes

External stimulus Responsive membrane Recognition - Conformational change Functions... 

Previously, pharmacologists were constrained to the prewired sensitivity of isolated tissues for agonist study. As discussed in Chapter 2, different tissues possess different densities of receptor, different receptor co-proteins in the membranes, and different efficiencies of stimulus-response mechanisms. Judicious choice of tissue type could yield uniquely useful pharmacologic systems (i.e., sensitive screening tissues). However, before the availability of recombinant systems these choices were limited. With the ability to express different densities of human target proteins such as receptors has come a transformation in drug discovery. Recombinant cellular systems can now... 

As noted above, Passmore et al. (2003) were the first to demonstrate that Kv7.2, 7.3 and 7.5 are expressed at the protein level in sensory neurons and also that functional M-currents can be measured under voltage-clamp. They were further able to demonstrate that pharmacological activation of Kv7 channels by direct application of retigabine to the spinal cord inhibited both C fiber and AS fiber-mediated signaling. This was true when the afferent fibers were excited by either electrical or tactile stimuli. Moreover, wind-up , an increased sensitivity of the stimulus/response relationship to repetitive stimuli, is also inhibited. These results demonstrate a clear role of Kv7 channels in sensory neuron processing. Gerlach et al. (2006, 2007) have also reported direct effects of ICA-27243 on both M-currents and membrane potential in isolated DRG neurons. Activation of the M-current by ICA-27243... 

Cartwright J, Hampton KK, Macneil S, Colvin BT, Preston FE. A haemorrhagic platdet disorder associated with altered stimulus-response coupling and abnormal membrane phosfdiolipid composition. Br JHaem. 1994 88 129-136. 

Roth et al. [80] proposed a method to determine the state of membrane wear by analyzing sodium chloride stimulus-response experiments. The shape of the distribution of sodium chloride in the permeate flow of the membrane revealed the solute permeation mechanisms for used membranes. For new membranes the distribution of sodium chloride collected in the permeate side as well in the rejection side was unimodal. For fouled membranes they noted the presence of several modes. The existence of a salt leakage peak, as well as an earlier detection of salt for all the fouled membranes, gave evidence of membrane stmcture modification. The intensive use of the membranes might have created an enlargement of the pore sizes. Salt and solvent permeabilities increased as well. While this is a difficult paper to follow, it may be of use to those who want to develop new methods for measuring membrane degradation. 

Roth E.M., Kessler, F.B., and Accary A., Sodium chloride stimulus-response experiments in spiral wound reverse osmosis membranes A new method to detect fouUng. Desalination 121 1999 183-193. 

In addition to the assessment of pore sizes and quality control, AFM provides direct access to the dynamic changes of smart pores, for instance pores that are equipped with a stimulus-responsive coating. Iwata et al. reported on the pH control of pore opening and closing of poly (acrylic acid) (PAA) -functionalized pores, as shown in Fig. 3.83. [174] The pores of two different membranes are closed, as seen by CM-AFM, at high pH due to the deprotonation of the PAA coating and concomitant expansion of the polymeric layer into the opening of the pore. 

Mechanism for stimulus-response coupling of photon absorption to the closure of plasma membrane cation channels. I, Inhibitory subunit of phosphodiesterase. 

Roth et al. [95] proposed a method to determine the state of membrane wear by analyzing sodinm chloride stimulus-response experiments. The shape of the distribntion of sodium chloride in the permeate flow of the membrane revealed the solnte permeation mechanisms for used membranes. For new manbranes, the distribution of sodium chloride collected in... 

Stimulus-responsiveness of the membrane is a specific property that is important in drug delivery systems in the presence of stimuli [e.g. the acidic environment of a tumor) the membrane is disrupted or changes its architecture e.g. from vesicle to micelle). Responsiveness of hydrophobic blocks can be chemically achieved for various stimuli, such as pH, redox conditions, enzyme-degradation, light, temperature, and changes in a magnetic field. ... 

Lipid-bilayer membranes on solid substrates are often used as cell-surface models connecting biological and artificial materials. They can be placed either directly on solids or on ultrathin polymer supports, such as brushes or hydrogels, which mimic the extracellular matrix. A similar approach has been applied to polymer membranes with the advantage of tunable thickness, easier chemical modifications to allow stimulus responsiveness, or the attachment of active molecules by incorporation of reactive end groups. In addition, incorporated proteins have lower interactions with the support because of the increased membrane thickness, and therefore behave as in a natural environment. ... 

If the liposomes in question are treated with the polymer after their formation, the polymer binds only to the outer surface of the liposomes. If the liposomes are formed from a lipid-polymer mixture, on the other hand, the polymer is present on both sides of the liposome membrane. Such liposomes respond even faster to temperature changes. The change of the liposome surface properties caused by the phase transition of stimulus-responsive polymers in also known to affect their interaction with cells. The phenomenon has been used in an attempt to develop a targeted drug delivery system. Liposomes modified with a pH-sensitive polymer, namely succinylated poly(glycidol), were shown to deliver the dye cacein more efficiently into cultured monkey kidney cells than nonmodified liposomes. ... 

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