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Biophysical studies of membrane proteins/peptides. Interaction with ...

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OUTLINE<br />

OUTLINE<br />

The last two decades, through a massive collective effort, allowed some insight into<br />

the nature <strong>of</strong> the interactions between the components <strong>of</strong> bio<strong>membrane</strong>s and also the<br />

highly relevant biological consequences <strong>of</strong> these interactions. The Singer-Nicolson fluid<br />

mosaic model for bio<strong>membrane</strong>s (1972), described a system where lipids were little else<br />

than a matrix where <strong>proteins</strong> were dispersed. The picture currently accepted is much<br />

more complex. Not only protein-protein interactions can be responsible for mediation <strong>of</strong><br />

cellular functions, but also protein-lipid interactions are much more complex and<br />

important than originally thought. Detailed biophysical <strong>studies</strong> such as the ones<br />

described here, allow gathering <strong>of</strong> valuable information regarding the character <strong>of</strong> such<br />

interactions.<br />

Bio<strong>membrane</strong>s delineate the boundaries <strong>of</strong> cellular life. They allow the<br />

differentiation <strong>of</strong> molecular environments through the control <strong>of</strong> permeability, creating<br />

the conditions for specialization <strong>with</strong>in the cell. This task demands the expenditure <strong>of</strong> a<br />

massive amount <strong>of</strong> energy, emphasizing the dramatic importance <strong>of</strong> bio<strong>membrane</strong>s.<br />

The foremost structural framework <strong>of</strong> bio<strong>membrane</strong>s is the lipid bilayer, but lipids<br />

are far from being a homogeneous class <strong>of</strong> molecules. When the energies <strong>of</strong> interaction<br />

between lipid molecules are significantly different, large scale phase separation <strong>of</strong> lipid<br />

molecules in the <strong>membrane</strong> can occur, and even for small differences in lipid-lipid<br />

interaction energies, short-range heterogeneities are expected. Therefore, the lateral<br />

distribution <strong>of</strong> a multicomponent lipid bilayer is <strong>of</strong>ten heterogeneous.<br />

This portrait <strong>of</strong> bio<strong>membrane</strong>s is made even more complex by the notion that lipids<br />

are not the only components found there. In fact, bio<strong>membrane</strong>s are a mixture <strong>of</strong><br />

different classes <strong>of</strong> molecules <strong>with</strong> different functions. Apart from lipids, the most<br />

notable component are <strong>proteins</strong>, which are highly concentrated in bio<strong>membrane</strong>s and<br />

are largely responsible for the cellular functions operated there.<br />

<strong>Interaction</strong>s between these quite different molecular species are very complex.<br />

Hydrogen bonds, electrostatic, and van der Waals forces, all operate simultaneously in<br />

dictating the equilibrium packing <strong>of</strong> <strong>proteins</strong> and lipids in bilayers. Notably, <strong>proteins</strong><br />

and lipids will arrange in such a manner that their hydrophobic domains are shielded<br />

from the aqueous environment in order to prevent the entropy loss resulting from<br />

interaction <strong>with</strong> water molecules. As a consequence, <strong>membrane</strong> <strong>proteins</strong> and lipids will<br />

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