Movement through the cell membrane
occurs in essentially two ways: passively, without an expenditure of energy, or
actively, using energy-consuming processes. The cell membrane can also engulf
a particle, forming a membrane-coated vesicle; this membrane-coated vesicle is
moved into the cell by endocytosis or out of the cell by exocytosis.
Passive Movement
Passive movement of particles or
ions across the cell membrane is directly influenced by chemical or electrical
gradients and does not require an expenditure of energy. A difference in the
number of particles on either side of the membrane creates a chemical gradient
and a difference in charged particle or ions creates an electrical gradient.
Chemical and electrical gradients are often linked and are called electrochemical
gradients.
Diffusion. Diffusion refers to the process by which
molecules and other particles in a solution become widely dispersed and reach a
uniform concentration because of energy created by their spontaneous kinetic
movements (Fig. 4.14A). Electrolytes and other substances move from an area of
higher to an area of lower concentration. With ions, diffusion is affected by
energy supplied by their electrical charge. Lipid-soluble molecules such as
oxygen, carbon dioxide, alcohol, and fatty acids become dissolved in the lipid
matrix of the cell membrane and diffuse through the membrane in the same manner
that diffusion occurs in water. Other substances diffuse through minute pores
of the cell membrane. The rate of movement depends on how many particles are
available for diffusion and the velocity of the kinetic movement of the
particles. The number of openings in the cell membrane through which the particles can move also determines
transfer rates. Temperature
changes the motion of the particles; the greater the temperature, the greater
is the thermal motion of the molecules. Thus, diffusion increases in proportion
to increased temperature.
Osmosis. Most cell membranes are semipermeable in that
they are permeable to water but not to all solute particles. Water moves
through water channels (aquaporins) in a semi-permeable membrane along a
concentration gradient, moving from an area of higher to one of lower
concentration (see Fig. 4.14B). This process is called osmosis, and the
pressure that water generates as it moves through the membrane is called osmotic
pressure.
Osmosis is regulated by the
concentration of nondiffusible particles on either side of a semipermeable
membrane. When there is a difference in the concentration of particles, water
moves from the side with the lower concentration of particles and higher
concentration of water to the side with the higher concentration of particles
and lower concentration of water. The movement of water continues until the
concentration of particles on both sides of the membrane is equally diluted
or until the hydrostatic (osmotic) pressure created by the movement of water
opposes its flow.
Facilitated Diffusion. Facilitated diffusion occurs through a
transport protein that is not linked to metabolic energy (see Fig. 4.14C). Some
substances, such as glucose, cannot pass unassisted through the cell membrane
because they are not lipid soluble or are too large to pass through the
membrane’s pores. These substances combine with special transport proteins at
the membrane’s outer surface, are carried across the membrane attached to the
transporter, and then released on the inside of the membrane. In facilitated
diffusion, a sub-stance can move only from an area of higher concentration to
one of lower concentration. The rate at which a substance moves across the
membrane because of facilitated diffusion depends on the difference in
concentration between the two sides of the membrane. Also important are the
availability of transport proteins and the rapidity with which they can bind
and release the substance being transported. It is thought that insulin, which
facilitates the movement of glucose into cells, acts by increasing the
availability of glucose transporters in the cell membrane.
Active Transport and Cotransport
Active transport mechanisms involve
the expenditure of energy. The process of diffusion describes particle movement
from an area of higher concentration to one of lower concentration, resulting
in an equal distribution across the cell membrane. Sometimes, however,
different concentrations of a substance are needed in the intracellular and
extracellular fluids. For example, to function, a cell requires a much higher
intracellular concentration of potassium ions than is present in the
extracellular fluid, while maintaining a much lower intra-cellular
concentration of sodium ions than the extracellular fluid. In these situations,
energy is required to pump the ions “uphill” or against their concentration
gradient. When cells use energy to move ions against an electrical or chemical gradient,
the process is called active transport.
The
active transport system
studied in the
greatest detail is the
sodium–potassium (Na+/K+)–ATPase pump (see Fig. 4.14D). This pump moves sodium from inside the cell to the extracellular region, the pump also
returns potassium to the inside, of the cell. Energy used to pump sodium out of
the cell and potassium into the cell is obtained by splitting and releasing
energy from the high-energy phosphate bond in ATP by the enzyme ATPase. Were it
not for the activity of the Na+/K+–ATPase pump, the
osmotically active sodium particles would accumulate in the cell, causing
cellular swelling because of an accompanying influx of water.
Two types of active transport
systems exist: primary active transport and secondary active transport. In primary
active transport, the source of energy (e.g., ATP) is used directly
in the transport of a substance. Secondary active transport mechanisms
harness the energy derived from the primary active transport of one substance,
usually sodium, for the cotransport of a second substance. For example, when
sodium ions are actively transported out of a cell by primary active transport,
a large concentration gradient develops (i.e., high concentration on the
outside and low on the inside). This concentration gradient represents a large
storehouse of energy because sodium ions are always attempting to diffuse into
the cell. Similar to facilitated diffusion, secondary transport mechanisms
use membrane transport proteins. These proteins have two binding sites, one for
sodium and the other for the substance undergoing secondary transport.
Secondary transport systems are classified into two groups: cotransport or
symport systems, in which the sodium ion and the solute are transported
in the same direction, and countertransport or antiport systems,
in which the sodium ion and the solute are transported in the opposite
direction (Fig. 4.15). An example of cotransport occurs in the intestine, where
the absorption of glucose and amino acids is coupled with sodium transport.
Endocytosis and Exocytosis
Endocytosis is the process by which cells engulf materials
from their surroundings. It includes pinocytosis and phagocytosis. Pinocytosis
involves the ingestion of small solid or fluid particles. The particles are
engulfed into small, membrane-surrounded vesicles for movement into the
cytoplasm. The process of pinocytosis is important in the transport of proteins
and strong solutions of electrolytes (see Fig. 4.14E).
Phagocytosis literally means “cell
eating” and can be compared with pinocytosis, which means “cell drinking.” It
involves the engulfment and subsequent killing or degradation of microorganisms
or other particulate matter. During phagocytosis, a particle contacts the cell
surface and is surrounded on all sides by the cell membrane, forming a phagocytic
vesicle or phagosome. Once formed, the phagosome breaks away from the cell
membrane and moves into the cytoplasm, where it eventually fuses with a
lysosome, allowing the ingested material to be degraded by lysosomal enzymes.
Certain cells, such as macrophages and polymorphonuclear leukocytes
(neutrophils), are adept at engulfing and disposing of invading organisms,
damaged cells, and unneeded extracellular constituents.
Receptor-mediated
endocytosis involves the binding of substances
such as low-density lipoproteins to a receptor on the cell surface. Binding of
a ligand (i.e., a substance with a high affinity for a receptor) to its
receptor normally causes widely distributed receptors to accumulate in clathrincoated
pits. An aggregation of special proteins on the cytoplasmic side of the pit
causes the coated pit to invaginate and pinch off, forming a clathrin-coated
vesicle that carries the ligand and its receptor into the cell.
Exocytosis is the mechanism for the secretion of intracellular
substances into the extracellular spaces. It is the reverse of endocytosis in
that a secretory granule fuses to the inner side of the cell membrane and an
opening is created in the cell membrane. This opening allows the contents of
the granule to be released into the extracellular fluid. Exocytosis is
important in removing cellular debris and releasing substances, such as
hormones, synthesized in the cell.
During endocytosis, portions of the
cell membrane become an endocytotic vesicle. During exocytosis, the vesicular
membrane is incorporated into the plasma membrane. In this way, cell membranes
can be conserved and reused.
Ion Channels
The electrical charge on small ions
such as sodium and potassium makes it difficult for these ions to move across
the lipid layer of the cell membrane. However, rapid movement of these ions is
required for many types of cell functions, such as nerve activity. This is
accomplished by facilitated diffusion through selective ion channels. Ion channels are integral proteins that span the width of the cell membrane and are
normally com- posed of several polypeptides or protein subunits that form a
gating system. Specific stimuli cause the protein subunits to undergo
conformational changes to form an open channel or gate through which the ions
can move (Fig. 4.16). In this way, ions do not need to cross the lipid-soluble
portion of the membrane but can remain in the aqueous solution that fills the
ion channel. Ion channels are highly selective; some channels allow only for
passage of sodium ions, and others are selective for potassium, calcium, or
chloride ions. Specific interactions between the ions and the sides of the
channel can produce an extremely rapid rate of ion movement. For example, ion
channels can become negatively charged, promoting the rapid movement of positively
charged ions.
The plasma membrane contains
two basic groups
of ion channels: leakage channels and gated channels. Leakage channels
are open even in the unstimulated state, whereas gated channels open and close
in response to specific stimuli. Three main types of gated channels are present
in the plasma membrane: voltage-gated channels, which have electrically
operated channels that open when the membrane potential changes beyond a
certain point; ligand-gated channels, which are chemically operated and
respond to specific receptor-bound ligands, such as the neurotransmitter
acetylcholine; and mechanically gated channels, which open or close in
response to such mechanical stimulations as vibrations, tissue stretching, or
pressure (see Fig. 4.16).
