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Structure and Functions of a Cell
Michael Wink
Heidelberg University, Institute of Pharmacy and Molecular Biotechnology (IPMB), Im Neuenheimer Feld 329, 69120 Heidelberg, Germany
3.1 Structure of a Eukaryotic Cell
3.1.1 Structure and Function of the Cytoplasmic Membrane
The hydrophilic or hydrophobic interactions of many lipid molecules in the aqueous cell environment give rise to the spontaneous formation of energetically favorable membrane bilayers. These are fluid, plastic, and mobile (Figures 2.2 and 3.1). Although the individual phospholipids spin around themselves and constantly move laterally, the resulting membrane is not easily permeable for ions, and charged or polar molecules.
Figure 3.1 Mobility of phospholipids in a biomembrane. Three types of movement are possible: rotation (spin), lateral diffusion, and flip‐flop, which occurs rarely. A flip‐flop can be brought about with the enzyme flippase.
Under cellular conditions, biomembranes tend not to lie flat like a carpet, but assume a spherical shape (Figure 3.2a). Should holes and ruptures in the cytoplasmic membrane occur, they are only transient and immediately resealed. These remarkable self‐organization and formation of supramolecular structures were prerequisites for the emergence of cells – and thus of life itself. Membranes can easily invert to form vesicles that, in turn, can merge with other membranes. When a vesicle is pinched off from a biomembrane, this is called exocytosis. When a vesicle is absorbed by a compartment membrane, it is called endocytosis.
Figure 3.2 Vesicle and liposome formation. (a) In an aqueous environment, lipid bilayers spontaneously form spherical vesicles, which makes them energetically favorable. (b) Schematic view of a liposome. Receptors, antibodies, and ligands may be integrated into the outside, which enables the liposome to recognize its target. Active compounds may be stored inside the liposome or bound outside of the membrane using nanoparticles or carrier molecules.
Small closed vesicles consisting of synthetic phospholipids are also called liposomes (Figure 3.2b). These play an important role in medicine and biotechnology, as they serve as vehicles for pharmaceutical compounds. They can be loaded with aggressive toxins. Researchers are trying to modify liposomes so that they can direct them to their targets via receptors or antibodies that are embedded in the liposomal membrane (see Chapter 26). This could prevent chemotherapeutics, such as those used in cancer therapy, from attacking and damaging healthy cells.
Cellular membranes have an asymmetric structure. Their building blocks on the inside of the cell differ from those on the outside (Figure 3.3). Due to the presence of negatively charged phosphatidylserine, the inside of a membrane is negatively charged. Biomembranes owe their specificity to the integration of certain membrane proteins and lipids. In the ER, new membrane sections are synthesized, allowing for their asymmetric structure. The enzyme flippase has an additional role to play in this context – facilitating a change of orientation in individual phospholipids (Figure 3.1).
Figure 3.3 Asymmetric structure of biomembranes.
3.1.1.1 Membrane Permeability
Biomembranes serve primarily as permeability barriers. The lipophilic inside of the membrane is an effective barrier against the diffusion of polar and charged substances, while membrane proteins enable the controlled import and export of ions and metabolites. The effectiveness of the membrane as a permeability barrier becomes apparent when looking at the difference in ion concentrations inside and outside a cell (Table 3.1). The differences in ion concentration may be as large as several powers of 10.
Table 3.1 Ion concentrations inside mammalian cells and in the extracellular space.
| Ion | Intracellular concentration | Extracellular concentration |
|---|---|---|
| Cations | ||
| Na+ | 5–15 mM | 145 mM |
| K+ | 140 mM | 5 mM |
| Mg++ | 0.5 mMa) | 1–2 mM |
| Ca++ | 100 nMa) | 1–2 mM |
| H+ | 10−7.2 M(=pH 7.2) | 10−7.4 M(=pH 7.4) |
| Anions | ||
| Cl− | 5–15 mM | 110 mM |
a) Ca++ and Mg++ also occur bound to proteins within the cell (1–2 mM or 20 mM, respectively).
Figure 3.4 shows a schematic view of the barrier function, using the example of an artificial lipid bilayer. Given sufficient time, any substance will diffuse through a membrane. The diffusion rate, however, varies considerably, depending on size, charge, and lipophilic properties of a molecule. The smaller and more hydrophobic a molecule is, the faster it will diffuse across a cell membrane. The following rules apply:
Smaller nonpolar molecules such as O2, CO2, and N2 are lipid soluble, diffusing rapidly through biomembranes. This is also true for lipophilic organic molecules such as benzene or chloroform. Many therapeutics are strongly lipophilic and can thus diffuse freely into the body.
Small uncharged