The cell membrane is a dynamic boundary that defines a cell, and proteins manage its functions, such as transport, signaling, and adhesion. Membrane proteins are molecules embedded in or temporarily associated with this boundary. The question of whether these proteins are hydrophobic, or water-repelling, is complex because their structure is dictated by their environment. The degree of hydrophobicity depends entirely on where a specific protein, or part of a protein, is located relative to the membrane’s structure. Understanding the chemical nature of the membrane itself is the first step in determining the properties of the associated proteins.
Understanding the Lipid Bilayer
The cellular environment, both inside the cell (cytosol) and outside the cell (extracellular space), is predominantly water-based, or aqueous. The cell membrane, known as the plasma membrane, separates these two environments by forming a lipid bilayer. This bilayer is constructed from specialized molecules called phospholipids, which are amphipathic. This means they have both a hydrophilic (water-loving) part and a hydrophobic (water-fearing) part.
The hydrophilic portions are the phosphate-containing heads, which are polar and readily interact with the surrounding water molecules on both the inner and outer surfaces. Conversely, the hydrophobic portions consist of two long, non-polar fatty acid tails. These tails spontaneously aggregate in the interior of the membrane, shielded from the aqueous environment. This arrangement creates an interior core that is highly nonpolar and intensely hydrophobic.
The resulting structure is a barrier where the surfaces are aqueous and polar, but the core is oily and nonpolar. This hydrophobic core dictates the chemical properties that any protein must possess to reside within the membrane. This necessity forces proteins that span the membrane to accommodate the nonpolar environment to remain stable and functional.
Integral Proteins and Hydrophobic Segments
Integral membrane proteins are permanently associated with the lipid bilayer, often spanning the entire width of the membrane. Because these proteins must pass through the hydrophobic core, they require specialized segments composed of hydrophobic amino acids. These segments are known as transmembrane domains, which anchor the protein securely within the membrane structure.
The amino acid side chains within these transmembrane domains are predominantly nonpolar. This enables them to form stable, non-covalent interactions with the surrounding fatty acid tails of the phospholipids. This pairing of nonpolar protein segments with the nonpolar lipid environment is thermodynamically favorable and prevents the protein from being expelled into the aqueous regions. A common structure for these segments is an alpha helix, which requires a sequence of about 19 to 23 hydrophobic amino acids to completely span the membrane.
The parts of the integral protein exposed to the aqueous environments (cytosol or extracellular space) are composed of hydrophilic amino acids. Therefore, many integral proteins are amphipathic, possessing both hydrophobic and hydrophilic regions. This dual nature allows the protein to be stably anchored in the nonpolar core while performing functions, like signaling or transport, in the aqueous exterior. The only way to remove these proteins is by using detergents, which mimic the lipid environment and disrupt the stabilizing hydrophobic interactions.
Peripheral Proteins and Surface Attachment
In contrast to integral proteins, peripheral proteins adhere only temporarily to the surface of the biological membrane. These proteins do not penetrate the hydrophobic core of the bilayer, residing entirely in the aqueous environment on either the inner or outer surface of the cell. Consequently, peripheral proteins are hydrophilic in nature, as they must readily interact with water.
Their attachment mechanisms rely on weaker, non-covalent interactions that do not require a strong hydrophobic anchor. Peripheral proteins often bind to the polar head groups of the phospholipids through ionic interactions or hydrogen bonds. They can also associate indirectly by binding to the hydrophilic regions of integral membrane proteins that protrude from the bilayer.
Because these attachments are weaker, peripheral proteins are relatively easy to dissociate from the membrane without destroying the bilayer structure. Changing the salt concentration or the pH of the surrounding solution can disrupt the electrostatic attractions and release the protein. This temporary and reversible attachment allows peripheral proteins to act as regulatory subunits for cell signaling and other transient cellular events. Peripheral proteins are polar molecules that favor the aqueous surroundings, unlike the hydrophobic segments of integral proteins.