Molecular Biology of the Cell

1. Cells Share Universal Features: DNA, RNA, Proteins, and Energy

All living cells on Earth store their hereditary information in the form of double-stranded molecules of DNA—long, unbranched, paired polymer chains, formed always of the same four types of monomers.

Fundamental Unity. Despite the vast diversity of life, all cells share a common set of features, highlighting the underlying unity of life on Earth. These include:

• DNA as the universal carrier of genetic information
• RNA as an intermediary in gene expression
• Proteins as the workhorses of the cell, catalyzing reactions and providing structure
• The need for free energy to maintain order and drive cellular processes

DNA's Central Role. DNA, with its four nucleotide bases (A, T, C, G), serves as the blueprint for all life. This double-stranded molecule replicates itself through templated polymerization, ensuring accurate transmission of hereditary information. RNA, transcribed from DNA, acts as a messenger, carrying genetic instructions to the protein synthesis machinery.

Proteins as Catalysts. Proteins, composed of amino acids, are the primary catalysts and structural components of cells. They perform a wide range of functions, from enzymatic reactions to molecular transport. All cells require a constant input of free energy, obtained from food or sunlight, to maintain their complex organization and drive essential biochemical processes.

2. Life's Diversity Springs from Genome Variations and Evolutionary History

Some genes evolve rapidly; others are highly conserved.

Three Domains of Life. The tree of life branches into three primary domains: Bacteria, Archaea, and Eukaryotes. While prokaryotic cells (Bacteria and Archaea) are generally smaller and simpler, they exhibit greater biochemical diversity than eukaryotic cells.

Genome Size and Evolution. Eukaryotic genomes are significantly larger and more complex than prokaryotic genomes, containing more regulatory DNA and noncoding sequences. New genes arise from preexisting ones through mutation, gene duplication, DNA segment shuffling, and horizontal gene transfer.

Molecular Clock. By comparing DNA sequences, scientists can construct phylogenetic trees that trace the relationships of all organisms. The rate of DNA sequence change acts as a molecular clock, providing insights into the timing of evolutionary events.

3. Eukaryotic Cells: A Symphony of Compartments and Genetic Complexity

Eukaryotic cells may have originated as predators.

Organelles and Complexity. Eukaryotic cells are distinguished by their membrane-enclosed organelles, including the nucleus, endoplasmic reticulum, Golgi apparatus, mitochondria, and lysosomes. These compartments create specialized environments for various cellular processes.

Endosymbiotic Theory. Mitochondria and chloroplasts are believed to have originated from symbiotic bacteria engulfed by ancestral eukaryotic cells. This endosymbiotic theory is supported by the presence of their own genomes and bacterial-like ribosomes.

Eukaryotic Genomes. Eukaryotic genomes are larger and more complex than prokaryotic genomes, containing more regulatory DNA and noncoding sequences. This complexity allows for more sophisticated control of gene expression and the development of multicellular organisms.

4. Proteins: The Architects of Cellular Form and Function

The shape of a protein is specified by its amino acid sequence.

Amino Acid Sequence. Proteins are long chains of amino acids linked by peptide bonds, folding into unique three-dimensional structures determined by their amino acid sequence. These structures are stabilized by noncovalent bonds and hydrophobic interactions.

Common Folding Patterns. The α helix and β sheet are common folding patterns found in proteins, arising from hydrogen bonding between the polypeptide backbone. Protein domains are modular units from which larger proteins are built, often associated with specific functions.

Protein Families. Proteins can be classified into families based on sequence and structural similarities, reflecting their evolutionary relationships. The human genome encodes a complex set of proteins, revealing that much remains unknown about protein function.

5. Enzymes: Nature's Catalysts Orchestrating Life's Chemistry

Enzymes speed reactions by selectively stabilizing transition states.

Enzymes and Metabolism. Enzymes are biological catalysts that speed up chemical reactions in cells, organizing cell metabolism into specific pathways. They lower the activation energy barriers that block chemical reactions, enabling them to occur at physiological temperatures.

Enzyme Mechanisms. Enzymes bind to substrates, forming enzyme-substrate complexes, and selectively stabilize transition states. They can use simultaneous acid and base catalysis to accelerate reactions.

Regulation of Enzyme Activity. Cells regulate enzyme activity through allosteric regulation, phosphorylation, and protein complex formation. These mechanisms allow cells to respond to changing conditions and maintain metabolic balance.

6. Gene Control: Orchestrating the Symphony of Life

The Different Cell Types of a Multicellular Organism Contain the Same DNA.

Gene Expression Control. Gene expression can be regulated at many steps, from DNA to RNA to protein. Transcription regulators, which bind to specific DNA sequences, play a central role in controlling gene expression.

Transcription Regulation. Transcription regulators can switch genes on or off, working in groups to control gene transcription in eukaryotes. Combinatorial gene control creates many different cell types.

Epigenetic Mechanisms. Epigenetic mechanisms, such as DNA methylation and chromatin modifications, reinforce cell memory in plants and animals, ensuring that stable patterns of gene expression can be transmitted to daughter cells.

7. Analyzing Cells: A Toolkit for Unveiling Life's Secrets

Cells Can Be Isolated from Tissues.

Cell Isolation and Culture. Cells can be isolated from tissues and grown in culture, providing accessible systems to study cell functions. Eukaryotic cell lines are a widely used source of homogeneous cells.

Protein Purification. Proteins can be separated by chromatography, immunoprecipitation, and genetically engineered tags. Purified cell-free systems are required for the precise dissection of molecular functions.

DNA Analysis. Restriction nucleases cut large DNA molecules into specific fragments, which can be separated by gel electrophoresis. Genes can be cloned using bacteria or PCR.

8. Visualizing Cells: Illuminating the Microscopic World

The Light Microscope Can Resolve Details 0.2 μm Apart.

Light Microscopy. The light microscope can resolve details 0.2 μm apart, allowing visualization of cells and their major components. Phase-contrast and differential-interference-contrast microscopy enhance the visibility of living cells.

Fluorescence Microscopy. Specific molecules can be located in cells by fluorescence microscopy, using antibodies or fluorescently tagged proteins. The confocal microscope produces optical sections by excluding out-of-focus light.

Electron Microscopy. The electron microscope resolves the fine structure of the cell, requiring special preparation techniques. Specific macromolecules can be localized by immunogold electron microscopy.

9. Membrane Structure: A Dynamic Foundation for Cellular Life

Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes.

Lipid Bilayer. Cell membranes are composed of a lipid bilayer, primarily formed by phospholipids, sphingolipids, and sterols. Phospholipids spontaneously form bilayers, creating a two-dimensional fluid structure.

Membrane Proteins. Membrane proteins can be associated with the lipid bilayer in various ways, including transmembrane α helices and lipid anchors. Many membrane proteins diffuse in the plane of the membrane, and cells can confine proteins and lipids to specific domains within a membrane.

Asymmetry. The asymmetry of the lipid bilayer is functionally important, with glycolipids found on the surface of all eukaryotic plasma membranes. The cortical cytoskeleton gives membranes mechanical strength and restricts membrane protein diffusion.

10. Membrane Transport: Gatekeepers of the Cell

Protein-Free Lipid Bilayers Are Impermeable to Ions.

Principles of Membrane Transport. Protein-free lipid bilayers are impermeable to ions. There are two main classes of membrane transport proteins: transporters and channels.

Transporters and Active Transport. Active transport is mediated by transporters coupled to an energy source. Transporters in the plasma membrane regulate cytosolic pH.

Channels and Electrical Properties. Channels are ion-selective and fluctuate between open and closed states. The membrane potential in animal cells depends mainly on K+ leak channels and the K+ gradient across the plasma membrane.

11. Cell Signaling: Communication and Coordination

Extracellular Signals Can Act Over Short or Long Distances.

Principles of Cell Signaling. Extracellular signals can act over short or long distances. Extracellular signal molecules bind to specific receptors.

GPCRs. Trimeric G proteins relay signals from GPCRs. Some G proteins regulate the production of cyclic AMP.

Enzyme-Coupled Receptors. Activated receptor tyrosine kinases (RTKs) phosphorylate themselves. The GTPase Ras mediates signaling by most RTKs.

12. The Cytoskeleton: Structure, Movement, and Organization

Cytoskeletal Filaments Adapt to Form Dynamic or Stable Structures.

Cytoskeleton Function and Origin. Cytoskeletal filaments adapt to form dynamic or stable structures. The cytoskeleton determines cellular organization and polarity.

Actin and Actin-Binding Proteins. Actin subunits assemble head-to-tail to create flexible, polar filaments. Actin-binding proteins influence filament dynamics and organization.

Microtubules. Microtubules are hollow tubes made of protofilaments. Microtubules undergo dynamic instability.

13. Cells in Their Social Context: Junctions, Matrix, and Cancer

Cadherins Form a Diverse Family of Adhesion Molecules.

Cell-Cell Junctions. Cadherins form a diverse family of adhesion molecules. Tight junctions form a seal between cells and a fence between plasma membrane domains.

Extracellular Matrix. The extracellular matrix is made and oriented by the cells within it. Glycosaminoglycan (GAG) chains occupy large amounts of space and form hydrated gels.

Cell-Matrix Junctions. Integrins are transmembrane heterodimers that link the extracellular matrix to the cytoskeleton. Extracellular matrix attachments act through integrins to control cell proliferation and survival.

Last updated: April 17, 2025