Transmembrane transport membrane pores

The first method employs the ballistic gun (2,3), where cells are exposed to ballistic bombardment by microparticles coated with the molecules of choice (e g., DNA). The second method is based on exposing the cells to ultrasound leading to an increased transmembrane transport (4). The third approach is based on an electrically driven process (electroporation), where cells are exposed to high-electric fields for short durations of micro- to milliseconds (5). This exposure leads to induction of short-lived permeability changes in the membrane ( pores ) enabling the diffusion of molecules across the membrane along their electrochemical gradients. 

Here we suggest that ions or molecules temporarily bound to the membrane surface may have their transmembrane movement enhanced by pore formation and that this possible mechanism also has catalytic features. This additional hypothesis envisions that local membrane conformational changes can result from both the local transmembrane voltage and the surface binding of a transported molecule (S). That is, a pore-substrate complex is formed. One possible outcome is transmembrane transport in which S is temporarily bound to the inner surface of a pore, with subsequent electrical lateral motion (relative to the pore inner surface) by diffusion or lateral drift to the other side. Alternatively, as a pore shrinks and closes, S is presented to the other side of the membrane. In either case, upon dissociation, transport of S will have been accomplished. 

RO membranes are characterized by a MWCO of 100 Da, and the process involves transmembrane pressures (TMPs) of 10-50 bar, which are 5-10 times higher than those used in UF [11,36]. Unlike UF, the separation by RO is achieved not by the size of the solute with respect to the membrane pore size but due to a pressure-driven solution-diffusion process [36]. In their early development, like UF membranes, RO membranes were uniquely structured films from synthetic organic polymers and consisted of an ultrathin skin layer superimposed on a coarsely porous matrix [3]. The skin layer of the RO membrane is nonporous, which may be treated as a water-swollen gel, and water is transported across membrane by dissolving in this gel and diffusing to the low-pressure side [3]. In the dairy industry, RO is used to concentrate milk or whey by removal of water and ionized minerals [11]. 

It is well documented that the surface chemistry and morphology of the membranes play an important role in the transmembrane transport of permeates (Khayet and Matsuura 2003a,b). To enhance the overall performance of a membrane, it is often necessary to modify the membrane material or its structure. Generally, the objective of modification is not only to increase the flux and/or selectivity, but also to control the pore size, eliminate defects, and improve the chemical resistance, for example, the solvent resistance, swelling, or fouling resistance. 

About 10 years ago, a new, easy and versatile technique for the introduction of larger macromolecules into eukaryotic and prokaryotic cells was established (Neumann et al., 1982 Knight, 1981) it is now commonly known as electroporation (Weaver, 1993). It is mainly a physical process, based on the transient permeabiliza-tion of cell membranes by pulses of sufficiently high electric fields. The underlying membrane phenomenon, called reversible electrical breakdown (REB) followed by transient pore formation, occurs if the transmembrane potential reaches values of 0.5 -1.5 V. Membrane pores are generated and molecules are transported through these pores by diffusion, electrical drift, and electroosmosis. Electroporation seems to be a rather universal process in most natural membranes. 

Membrane active natural ion transporters are the prime source of inspiration for the design of synthetic transmembrane transporters. These compounds are valuable examples of self-sorting systems to construct functional membrane spanning pores and transporter ion interactions to facilitate the passage of ions across the membrane. 

This selective transport across cellular membranes is carried out by two broad classes of specialized proteins, which are assodated with or embedded in those lipid bilayers channels and transmembrane transporters. They work by different mechanisms Whereas channels catalyze the passage of ions (or water and gas in the case of the aquaporin channel) (Agre, 2006) across the membrane through a watery pore spanning the membrane-embedded protein, transporters are working via a cycle of conformational changes that expose substrate-binding sites alternately to the two sides of the membrane (Theobald Miller, 2010). 

Chromatin condensation membrane blebbing release of cytochrome c through the permeability transition pore complex activation of caspases Disruption of cytoplasmic membrane and other organelles (e.g., lysosomes, Golgi apparatus) drastic alteration of transmembrane transport processes inhibition of protein synthesis... 

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

Three types of membrane transporter are found channels, carriers and pumps (Fignre 6.10). Channels are transmembrane proteins that function as selective pores throngh which ions or uncharged molecules can diffuse passively. Their selectivity for solutes depends on the size of the pore and the density of surface charges lining it. These are altered in response to external and internal stimuli in the plant, so regnlating the transport. 

Gurtovenko, A.A., Vattulainen, I. Pore formation coupled to ion transport through lipid membranes as induced by transmembrane ionic charge imbalance atomistic molecular dynamics study. J. Am. Chem. Soc. 2005, 127, 17570-1. 

Much progress has been made in understanding the different mechanisms that can cause mitochondrial dysfunction, such as (i) uncoupling of electron transport from ATP synthesis by undermining integrity of inner membrane (ii) direct inhibition of electron transport system components (iii) opening of the mitochondrial permeability transition pore leading to irreversible collapse of the transmembrane potential and release of pro-apoptotic factors (iv) inhibition of the... 

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