Basic Cell and Molecular Biology

Click to identify major components of the cell above:

Cells have an ultrastructure that is composed of several key elements.

  • Plasma membrane: a basic cell is bounded by a cell membrane which consists of a lipid bilayer (a combination of phospholipids and proteins) that provides a barrier to diffusion of ionic compounds. Glycolipids and cholesterol are also present in the membrane. Within the membrane are various proteins that function in cell transport, binding, and recognition.

    • Transmembrane proteins can form ion channels for transport of substances across the membrane, often controlled by signalling molecules that change the protein conformation to open or close the channels. Most of these channels are thus "gated" and opened by a signalling mechanism, such as: voltage depolarization with nerve conduction, neurotransmitters such as acetylcholine, nucleotides such as cyclic AMP, or stereocilia.

    • Carrier proteins that specifically bind to substances, undergoing reversible conformational change, can cross the plasma membrane.

    • The sodium pump, powered by ATP, maintains the concentration of potassium ion much higher inside the cell while transporting sodium out of the cell to reduce intracellular osmotic pressure.

    • On the outer membrane surface are carbohydrates that for the glycocalyx surronding the cell, providing protection, adhesion, and antigen recognition for immune functions. Antigenic components of the glycocalyx form the basis for blood typing of red blood cells.

  • The cell membrane bounds the cell cytoplasm that contains the cytosol and a variety of organelles that also have membranes dividing them from other cellular components.

    • Lipid membranes are formed by the smooth endoplasmic reticulum of the cell and proteins within the lipid bilayer are synthesized by rough endoplasmic reticulum.

    • Specialized parts of membranes can include junctional complexes such as desmosomes and tight junctions that provide adhesion between cells, or gap junctions (intercellular pores) that provide signalling pathways between cells. Some epithelial cells may have projections called microvilli that increase surface area. Membrane receptors consist of specialize proteins that are present in pits which provide for invagination and pinocytosis to bring substances into the cell. Endosomes are membrane bound structures that aid in transporting pinocytotic vesicles further into the cell.

    • Cell surface receptors provde a means for large signalling molecules to act upon the cell. Most receptors are glycoproteins. Many receptors are G-protein linked and function via GTPases to activate (GS) or deactivate (G1) adenylate cyclase, which transforms ATP to cyclic AMP. c-AMP is the most common "second messenger" that provides intracellular signalling following receptor binding by another substance. Signaling via GP activates phospholipase C to release calcium ion and activate protein kinase C, which starts phosphorylation to activate gene regulatory proteins that initiate specific gene transcription to control cell function.

    • Calmodulin is a protein found in many cells and binds excess calcium ion. The calmodulin-Ca++ complex activates calmodulin dependent protein kinases that regulate some cell functions.

  • Ribosomes: these small dot-like structures contain protein and ribosomal RNA. There are binding sites for tRNA (each bonding to its own specific amino acid and having the anticodon corresponding to an mRNA codon) that are directed to transcribe proteins via coded instructions in the codons of mRNA.

  • Endoplasmic reticulum (ER): this structure is classified into smooth endoplasmic reticulum (SER) when there are no attached ribosomes and rough endoplasmic reticulum (RER) when ribosomes are attached.

    • SER aids in the formation of plasma membranes through production of lipids (cholesterol and triglycerides). SER functions in steroid hormone synthesis in endocrine cells. In hepatocytes, SER aids in detoxification pathways.

    • RER is the major protein synthetic factory of the cell. Ribosomes are structures in which mRNA from the nucleus attaches to direct protein synthesis. The RER forms the lipids and proteins that make up cell membranes. RER forms all proteins transported out of the cell. Proteins are also modified here by glycosylation, sulfation, and conformation. Proteins to be packaged for delivery have a signal peptide that contacts a signal recognition particle to provide transport into the RER cisterna.

  • Golgi apparatus: this structure is a stack of cisternae and represents a "finishing shop" that takes pre-manufactured lipids and proteins and modifies them by adding or deleting carbohydrates. The finished products either fuse with endosomes to remain in the cell or are packaged as secretory vesicles for transport out of the cell.

  • Endosomes and Lysosomes: these organelles participate in the ingestion of materials into the cell. Cellular ingestion of material outside the cell is called endocytosis. If the particles are large, and a large vesicle is required, the process is called phagocytosis; for small particles in small vesicles it is called pinocytosis.

    • Pinocytosis functions to recycle portions of cell membrane and to ingest small particles within vesicles. Cell membrane receptors aid the process. Clathrin molecules form a "basket" to catch the vesicle as it forms from an invaginated pit on the cell membrane. The vesicles fuse with endosomes. Endosomes deliver their contents by fusing with lysosomes. Enzymes within lysosomes digest the contents.

    • Phagocytosis is performed mostly by inflammatory cells, macrophages in particular, to clear debris and to destroy infectious micro-organisms. The cell moves to engulf the particle and form a phagosome that fuses with a lysosome, and enzymes degrade the material. Non-digestible lipids may remain, and a "residual body" is left.

    The lysosomal enzymes come from RER processed through the Golgi. Lysosomal enzymes may be utilized to destroy bacteria phagocytosed by inflammatory cells. Lysosomes may be part of cell recycling and renovation.

  • Peroxisomes: an organelle similar to a lysosome is known as a peroxisome. They contain enzymes important in oxidation-reduction reactions in some cells, particularly in catabolism of long chain fatty acids and in formation of hydrogen peroxide. Hydrogen peroxide functions in detoxification and in microbial killing.

  • Mitochondria: these organelles are the "powerhouses" of the cell that consume oxygen in oxidative phosphorylation to produce the ATP necessary for the energy to drive cellular metabolism. Their inner membranes are convoluted into cristae to increase surface area. The outer mitochondrial membrane has holes calld porins through which small proteins can pass. The inner mitochondrial membrane is folded to form the cristae and enclose a matrix space; it is highly impermeable due to the presence of cardiolipin.

    Protein complexes called the electron transport chain on the inner membrane form a proton pump to transport hydrogen ion from the matrix to the intermembrane space to power the ATP synthase of the inner membrane. Small dense matrix granules bind excess calcium ion that may damage mitochondria when the cell is injured. The inner and outer mitochondrial membranes come together at contact points where carrier proteins transport other proteins in and out of the mitochondrion.

    More metabolically active cells have more mitochondria. Mitochondria have their own DNA (in a circular strand), which is inherited from your mother, and are self-replicating.

  • Cytoskeleton: the cytoplasm contains a variety of structure components that provide for cellular support and movement. These structures can include: microtubules, microfilaments, and intermediate filaments. The intermediate filaments can include components such as cytokeratins (in epithelial cells), desmin (in muscle), vimentin (in connective tissues), neurofilaments (in nervous system), and glial fibrillary acidic protein (in glial cells of nervous system).

    Microtubules (comprised of proteins called tubulin) can form cilia, as seen in respiratory epithelium, centrioles at the base of cilia (basal bodies), and flagella, as seen in spermatozoa. Microtubules have positively and negatively charged ends and can function in transport of vesicles and organelles within the cell. The microtubule protein dynein transports vesicles to the negative end and the protein kinesin to the positive end.

    Microtubules that compose cilia make up an axoneme that has nine doublets surrounding two singlets of microtubles. The cilia are powered by dynein arms and anchored by a basal body. Basal bodies of cilia are similar to centrioles that form the spindle in mitosis (blocked by the drug colchicine). Centrioles have 9 triplets of microtubules.

    Microfilaments include the thin actin filaments and thick myosin filaments that are contractile proteins in muscle and other cells requiring movement. The microfilaments are mainly composed of f-actin, which makes up about 1/6 of the protein content of non-muscle cells. The intermediate filaments provide structural integrity and also provide a means for identifying cells by immunohistochemical staining with antibody to various intermediate filaments.

    Structural integrity of the cell is further maintained by a network of actin filaments with spectrin, forming a terminal web in the outer part of the cell. Integrin is a transmembrane protein that binds to fibronectin in the extracellular matrix to aid in attachment of the cell.

  • Nucleus: the nucleus contains the DNA that directs cellular function. In non-dividing cells, the DNA of the chromosomes is dispersed and appears as clumps of nucleoplasm. The DNA is intermixed with histone proteins that forms chromatin. The darker staining heterochromatin is inactive, while the lighter staining euchromatin is forming mRNA and directing cell functions. There is an inner and an outer nuclear membrane. The outer membrane connects to RER. Scattered nuclear pores provide a path from nucleus to cytoplasm.

    Humans have 46 chromosomes (23 pairs). Males have an X and a Y chromosome, plus 22 pairs of autosomes; women have two X chromosomes, one of which is inactive and clumped as a small "Barr body". Cells are diploid, with 23 pairs of chromosomes. The gametes (ova, sperm) from reproductive organs have undergone meiotic division to a haploid complement (23 single chromosomes).

  • Nucleolus: a nucleus may contain a smaller rounded dark structure known as a nucleolus that is composed predominantly of RNA. Nucleoli synthesize the cytoplasmic ribosomes.

Intercellular Ground Substances

  • A variety of materials make up the "ground substance" or "extracellular matrix" that lies between cells outside of their cell membranes. A variety of sulfated glycosaminoglycans such as keratan sulfate or heparan sulfate are present and they link to proteins to form proteoglycans. Many proteoglycans are attached to hyaluronic acid to form a resilient matrix that functions similar to the material in a seat cushion of a chair. The cells "sit" on the extracellular matrix and are cushioned by it. The electrical charge on these macromolecules can also act as a selective barrier when situated next to a basal lamina. Adhesive glycoproteins include fibronectin which binds to other extracellular macromolecules and to cellular integrin. Another adhesive glycoprotein found in basal lamina (basement membrane) beneath epithelial cells is laminin.

  • Much of the toughness and resilience of tissues is imparted by extracellular collagen. Collagen is formed in connective tissue cells such as fibroblasts that make procollagen which is transformed in the extracellular matrix to tropocollagen molecules that form alpha chains. Three chains are braided into a collagen rope that, like nylon rope, is both tough but also stretches. There are several types of collagen:

    • Type 1: found in bone

    • Type 2: found in elastic and hyaline cartilage

    • Type 3: found in reticulin fibers

    • Type 4: found in basement membranes

    • Type 5: found in a variety of connective tissues such as tendons

    • Type 7: found in anchoring fibrils of epithelial basement membrane

Cell Cycle

  • A cell that divides goes through several phases. Prior to dividing in mitosis, a cell goes through the G1, S, and G2 phases.

    • G1 phase: the cell synthesizes RNA, regulatory proteins, and enzymes which will provide for cell growth through synthesis of new cellular components.

    • S phase: the cell duplicates its genome with formation of new DNA to comprise twice the amount of DNA (in autosomal cells) in a resting cell.

    • G2 phase: DNA is repaired and the cell produces RNA and proteins needed for division.

    • M phase: the cell undergoes mitosis and divides in half.

  • Cells can be categorized by their relation to the cell cycle:

    • Stable cells have exited the cycle, never to return. These are fully differntiated cells such as neurons that remain through life.

    • Labile cells are quiescent (in G0) but able to re-enter the cell cycle if necessary. Such cells include connective tissues and hepatocytes.

    • Labile cells continue to divide and proliferate. Such cells include those in epithelia, the bone marrow, and germ cells (in males).