Biomedical Engineering Reference
In-Depth Information
2.6
Transport of Macromolecules
Tissue membranes offer routes between blood and tissue for the diffusion of mol-
ecules, which are attracted to lipids (lipophilic) and small-molecular-weight mol-
ecules, which are attracted to water (hydrophilic). For example, liver cells secrete
albumin, the principal blood plasma protein necessary for homeostasis. Everyday
nearly 2% of plasma albumin is replaced. The diffusion of albumin (see Exam-
ple 2.6) is significantly smaller than oxygen and other smaller molecules. Further,
vascular walls are impermeable to macromolecules such as large proteins, poly-
saccharides, or polynucleotides. This impermeability of microvascular walls is a
prerequisite for the establishment and maintenance of a fluid equilibrium between
the intravascular and extravascular fluid compartments. On the other hand, a large
number of other macromolecular substances must continually have access to the
interstitial space to be ultimately returned to the plasma via the lymphatic system.
This is of particular importance in inflammatory conditions and for immune re-
sponse. Transport of protein across the alveolar epithelial barrier is a critical pro-
cess in recovery from pulmonary edema and is also important in maintaining the
alveolar milieu in the normal healthy lung.
One strategy used by cells to selectively transport macromolecules is called
transcytosis, also referred to as vesicular transport. Membrane components such as
lipids and proteins are continuously transported from the Golgi complex to the cell
membrane through vesicles continuously. Transcytosis is of critical importance to a
number of physiological processes, including bone formation (endochondral ossi-
fication) and wound healing. Fibroblasts in the connective tissue secrete large pro-
collagen, which matures into collagen in the connective tissue, and transport using
transcytosis. Albumin is transported in large quantities through transcytosis. The
existence of transcytosis was first postulated by Palade in the 1950s. Transcytosis
involves the sequential formation and fusion of membrane-bounded vesicles. Cells
ingest molecules using a part of the cell membrane to form a vesicle. The substance
to be ingested is progressively enclosed by a small portion of the plasma membrane,
which first invaginates and then pinches off to form an intracellular vesicle con-
taining the ingested material. The process is called endocytosis. The nature of the
internalized constituents, either fluids or particles of different sizes, delineates the
various internalization processes. Based on the engulfed particle size, endocytosis is
referred as phagocytosis (cell eating), and pinocytosis (cell drinking).
Phagocytosis involves the entry of large particles, typically 1 mm or more, in-
cluding particles as diverse as inert beads, apoptotic cells, and microbes. The early
events leading to particle engulfment during phagocytosis is complex and involves
different mechanisms. In general, cells invaginate their cell surface to form a phago-
some and ingestion occurs in specialized regions, called caveolae, present within the
plasma membrane. A vacuole is formed that contains the engulfed material, which
is fused with the lysosome to be degraded or transported to other parts of the cells.
Specialized cells (also referred as phagocytes) such as neutrophils, dendritic cells,
and macrophages use phagocytosis as a mechanism to remove pathogens. Recogni-
tion of specific sites on the particle by cell-surface molecules of the phagocytes ini-
tiates the phagocytic process. Phagocytosis and the subsequent killing of microbes
