**7. Concluding remarks: design and modulation**

*Liposomes - Advances and Perspectives*

**22**

**Figure 17.**

**Figure 16.**

other biomolecules [19, 73].

*Orientation of CO groups at the bilayer interphase in relation to curvature.*

As described in **Figure 9**, carbonyl groups are one of the hydration centers in which interfacial water is distributed. The formation of high curvature surfaces is

*The curvature domains*, in fact, increases the bilayer free energy surface by exposing hydrophobic region and carbonyl configuration as observed in part B of **Figure 17**. The stabilization of peptides or amino acid is the result of the decrease of free energy at expense of the bending modulus, that is, the energy cost of topological changes [67, 71, 72]. This last quantity is an important parameter that governs a membrane's tendency for defect formation. Many kinds of defects may be formed, including vesicle budding and fusion, depending on the presence of non-bilayer lipid phases, cholesterol and interactions between lipid bilayers and

related to changes in the *CO arrangements* [39] (**Figure 17**).

*Defects induced by osmotic shrinkage enhance Phe insertion into lipid bilayers.*

*The lipid matrix in cell membranes presents a variety of lipids*. As shown in **Figure 18**, all of them present a diacyl glycerol structure with acyl chains differing in saturation and length, a phosphate group in position 3 linked to a proton, choline, ethanolamine, glycerol, serine or inositol residues. It is difficult to accept that within the economicity principle of biology, this wide variation does not play a role in *functional properties of the membrane.*

It must be noticed that all lipids may be aligned along a plane containing the glycerol backbone and the carbonyl groups. On one side of this plane, the hydrocarbon region can vary in terms of chain length, saturation and ramification. Each of these variations may give a complex matrix in which water cannot be excluded and constitute a media of a wide range of dielectric properties. On the other, polar groups protrude into the aqueous phase at different magnitudes. Importantly, also these groups are able in different extents to form hydrogen bonds between its lipid neighbors and with water. *In conclusion, it is an oversimplification to reduce the bilayer structure in which lipids organize facing the polar groups to water and segregating the nonpolar chains*.

The lack of details in these regions in relation to their emergent properties is a major limitation in the design of biomimetic systems that, as liposomes and vesicles, may be used for biotechnological and medical purposes. As a consequence, literature is saturated with works in which only "try and error" strategies are employed.

In this chapter, we have briefly discussed that:


#### **Figure 18.**

*Protrusion of the groups esterified to the phosphate in the surface of the membrane promotes different water organization.*

#### *Liposomes - Advances and Perspectives*

These studies indicate a deeper understanding of the role of lipid bilayers in cellular biology and support the development of future lipid-based biotechnology that should necessarily include the role of water as a membrane dynamic component.
