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Membrane fusion induced by small molecules and ions.

Mondal Roy S, Sarkar M - J Lipids (2011)

Bottom Line: Small molecules/ions do not share this advantage.Here we intend to present, how a variety of small molecules/ions act as independent fusogens.The detailed mechanism of some are well understood but for many it is still an unanswered question.

View Article: PubMed Central - PubMed

Affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, Sector 1, Block AF, Bidhannagar, Kolkata 700064, India.

ABSTRACT
Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes.

No MeSH data available.


Related in: MedlinePlus

Ibuprofen.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig12: Ibuprofen.

Mentions: The process of membrane fusion mediated by proteins/peptides is very different from that mediated by small molecules and ions. As we have already discussed, the basic difference that exists between these two types of fusion lies in their difference in the process of harnessing the energy required for overcoming the different intermediate steps of the fusion process. For protein/peptide-induced fusion, this energy is provided by the structural reorganization of the big molecules. Small molecules or ions do not have this advantage, as their structural reorganization is not expected to supply the required driving force. The mechanism for the process of fusion induced by small molecules/ions varies to some extent depending on the nature of the fusogen, though the basic steps of the fusion process remain similar. In general, small molecules get partitioned inside the membrane (or hydrophobic lipid phase) and cause a destabilization of the lipid bilayer. This destabilization manifests in membrane perturbation in different ways, depending on the nature of the small molecules. This perturbation may increase the permeability of the membranes, may make the collision between the vesicles more sticky, may increase the surface tension, or may even help in forming the inverted hexagonal phase (HII) formation. Any of these changes will help in inducing fusion. In case of ion-induced fusion, the primary effect is dependent on charge screening, where charge neutralization of the anionic lipid head groups by the cations promotes aggregation of the lipid vesicles and finally fusion occurs. However, in many cases, charge screening is found to be necessary but not a sufficient condition for the complete fusion. Additional factors like change in surface tension, surface hydration, and so forth, participate along with charge screening to lead the fusion to completion. This mechanism is different from the mechanism of small molecule-induced fusion as mentioned above. Table 2, shows the threshold concentration of small molecules that is required to trigger membrane fusion. This has been compared with their dimension. Significant correlation exists between the concentration of the small molecules required for destabilization of the membrane bilayer, with their dimension. Even though there exists a correlation between molecular dimension and concentration of destabilization, it is not the only decisive factor. Molecules having similar dimension like ibuprofen (Figure 12) do not show fusion [115].


Membrane fusion induced by small molecules and ions.

Mondal Roy S, Sarkar M - J Lipids (2011)

Ibuprofen.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108104&req=5

fig12: Ibuprofen.
Mentions: The process of membrane fusion mediated by proteins/peptides is very different from that mediated by small molecules and ions. As we have already discussed, the basic difference that exists between these two types of fusion lies in their difference in the process of harnessing the energy required for overcoming the different intermediate steps of the fusion process. For protein/peptide-induced fusion, this energy is provided by the structural reorganization of the big molecules. Small molecules or ions do not have this advantage, as their structural reorganization is not expected to supply the required driving force. The mechanism for the process of fusion induced by small molecules/ions varies to some extent depending on the nature of the fusogen, though the basic steps of the fusion process remain similar. In general, small molecules get partitioned inside the membrane (or hydrophobic lipid phase) and cause a destabilization of the lipid bilayer. This destabilization manifests in membrane perturbation in different ways, depending on the nature of the small molecules. This perturbation may increase the permeability of the membranes, may make the collision between the vesicles more sticky, may increase the surface tension, or may even help in forming the inverted hexagonal phase (HII) formation. Any of these changes will help in inducing fusion. In case of ion-induced fusion, the primary effect is dependent on charge screening, where charge neutralization of the anionic lipid head groups by the cations promotes aggregation of the lipid vesicles and finally fusion occurs. However, in many cases, charge screening is found to be necessary but not a sufficient condition for the complete fusion. Additional factors like change in surface tension, surface hydration, and so forth, participate along with charge screening to lead the fusion to completion. This mechanism is different from the mechanism of small molecule-induced fusion as mentioned above. Table 2, shows the threshold concentration of small molecules that is required to trigger membrane fusion. This has been compared with their dimension. Significant correlation exists between the concentration of the small molecules required for destabilization of the membrane bilayer, with their dimension. Even though there exists a correlation between molecular dimension and concentration of destabilization, it is not the only decisive factor. Molecules having similar dimension like ibuprofen (Figure 12) do not show fusion [115].

Bottom Line: Small molecules/ions do not share this advantage.Here we intend to present, how a variety of small molecules/ions act as independent fusogens.The detailed mechanism of some are well understood but for many it is still an unanswered question.

View Article: PubMed Central - PubMed

Affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, Sector 1, Block AF, Bidhannagar, Kolkata 700064, India.

ABSTRACT
Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes.

No MeSH data available.


Related in: MedlinePlus