Fundamentals of cellular & molecular biology
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A container for life, the cell Cells are defined as the smallest unit of self-sustaining life. Single cell organisms such as amoebas or bacteria are examples of how a whole being can exist as one unit. In contrast, the human body is composed of over thirty-trillion cells. The elegance of a dynamic organism is the result of differentiated cell types - cells develop with specific structures and functions to comprise complex organs within a whole body. Below, the characteristics of human cells are described.
Stable structures are built from a sturdy foundation and frame, and all cells have fundamental features. The boundary of the cell is a lipid bilayer - a cohesive membrane of individual phosopholipid molecules encircles the internal cell environment. Phospholipids consist of a polar (electrically charged, hydrophilic) head attached to a long lipid tail (no charge, hydrophobic). The polar head groups orient together in a chain and the lipid tails draw together to form two opposing layers which we refer to as the cell membrane. Imagine the fat that floats to the top of a jar of broth - these phospholipids assemble to form the cell’s surface, a barrier separating the intracellular components from the extracellular system creating an autonomous container.
The Cell and its organelles
The inside of the cell is not a disordered soup of molecules, but a mesh of structural elements organizing functional organelles within. Filaments - long thin proteins make up the cytoskeleton. Tubes and threads of protein attach to the interior of the cell membrane, spanning the sea of the cell, the cytosol. These filaments provide mechanical support and enable movement & growth.
The cell communicates, replicates, and transforms energy. Specialized organelles carry out these vital operations:
The Golgi complex, post office of the cell, receives molecules from the nucleus and packages them for destinations within the cell, or to be sent beyond the cell membrane.
Mitochondria metabolize carbohydrates and fatty acids into energy in the form of ATP (adenosine tri-phosphate), the prime cellular fuel.
Ribosomes read genetic instructions sent from the genome in the form of messenger RNA (mRNA) to build proteins.
The Nucleus is the largest organelle in the cell and contains the whole genome of DNA. Each cell in the body contains a copy of the complete DNA sequence coding for all cellular structures and functions necessary for life.
The above illustrates a sketch of what a cell is, but an organism is an exquisite orchestration of diverse cell types elegantly moving as one being.
The language of electrons Atoms are the basic building blocks of matter, consisting of a nucleus orbited by electrons. Elements are defined by the number of protons in the nucleus of an atom, 118 known elements form the matter of our reality. An atom with a positive or negative charge would respectively have lost or gained an electron, becoming an ion. Elements such as sodium, potassium, chloride, calcium, magnesium and phosphate are examples of biologically active ions. The transfer of an electron from one molecule to another has formidable energetic implications. The smallest molecules are the messengers of bodies.
A single carbon atom
A cell is not static, nor is it a closed system. Selective permeability of the cell membrane allows for a discerning flow of molecules across the barrier, and is how cells speak to each other to function collectively. Embedded in the membrane are proteins spanning from the intracellular cytosol to the extracellular space, some like tunnels through a mountain ridge, others rooted like sign posts. Protein channels facilitate the transport of molecules between cells, but do not do so freely. A stimulus such as electrical charge, temperature, or molecular signal will open the channel to intentionally moderate the transfer of a molecule.
Cells are electric. Different concentrations of positive and negative ions across the membrane of a cell create a gradient in charge - the membrane potential. Positive ions will flow with ease into regions higher in a negative charge, but to push against equilibrium comes at an energetic cost. Membrane proteins carefully balance ion concentrations. extracellular space, some like tunnels through a mountain ridge, others rooted like sign posts. Protein channels facilitate the transport of molecules between cells, but do not do so freely. A stimulus such as electrical charge, temperature, or molecular signal will open the channel to intentionally moderate the transfer of a molecule.
An ion channel
Powerful currents are conducted by ion gradients. Every sensation our bodies perceive is through the activation of neurons, specialized cells of the nervous system. Resting, neurons have an internal negative concentration gradient. When this gradient is depolarized an action potential triggers sodium channels to open, allowing a flow of positively charged sodium ions to come into the cell. Like dominos falling in line, the action potential sets off a rapid change in electrochemical gradient of the cell, depolarizing adjacent neurons propogating the electrical signal. Neurotransmitters are small molecules that can also depolarize neurons, triggering an action potential. Gentle touch on the skin stimulates tactile nerve fibers to release a neuropeptide activating a specialized bundle of neurons in the spinal column, sending a message of calming, pleasant touch to the brain (Liu).
Gap junctions are cell-to-cell membrane channels; spanning the space between cells forming direct intracellular channels for rapid exchange of ions. Functionally found in all cell types, but within the heart they play a pivotal role in impulse propagation of the heart tissue. As seen in neurons with sodium channels, gap junctions alongside sodium channels, moderate the conduction of a heart beat. Contracting myocytes (heart cells), a throbbing pulse cursing through our veins, ions the maestro. Gap junction channels allow for a continuous current to flow through the muscle tissue of the heart (Rohr).
The central dogmaDNA > Transcription > RNA > Translation > Protein At the center of it all, DNA (deoxyribonucleic acid). A molecular code for the building blocks of life. Nucleotides are molecules with a sugar-phosphate group attached to a unique nucleic acid. The phosphate groups form a back bone of the DNA chain, giving DNA a negative charge. Four nucleotide bases are the language of the genetic code: adenine (A), guanine (G), cytosine (C), thymine (T). The bases of two strands of single-stranded DNA chain preferentially pair together, A-T and G-C, forming base pairs. The double helix is two linked strands of DNA, a winding mirrored code. The entire human genome is roughly 3 billion base pairs long, split between 46 condensed pieces of DNA called chromosomes. Within the genome, there are specific sequences referred to as genes coding for proteins, a few hundred to millions of base pairs long.
A strand of DNA
How does a gene become a protein? Transcription factors (TFs) are proteins that bind to specific target sequences in the DNA strand, within or upstream of a gene, to activate transcription. TFs allows RNA Polymerase, a catalytic protein, to bind the promoter of a gene sequence and make a copy of mRNA. RNA is similar to DNA, but it is often single stranded and has slight differences in the composition of the nucleotide bases. The mRNA is transported out of the nucleus to a ribosome for protein translation. The ribosome reads the mRNA using a triplet code to translate the nucleotide sequence into amino acids, the building blocks of proteins. For example, CGG codes for the amino acid argenine, and a gene that is 150 bases long would translate to a peptide chain of 50 amino acids (Philips).
Transcription of a strand of DNA into RNA
There are 20 amino acids with various biochemical properties, and the polypeptide chain of a protein is generally 50-2000 amino acids long. A gentle dance transforms the polypeptide chain into a stable 3D form. Folding, winding, and stabilizing through internal interactions the linear chain becomes a dynamic protein. Protein folding is sensitive, influenced by environmental factors like temperature, pH, electric & magnetic fields. Mis-folded proteins can result in disease, Alzheimer’s is characterized by misfolded fibrillar B-amyloid proteins of the brain.
The physical form of the protein dictates function. Hemoglobin is a protein found in red blood cells that binds to oxygen and carbon dioxide. A chariot of the breath, delivering elemental air to every tissue and organ in the body. Myosin, actin, tropomyosin, and troponin are structural proteins that form the basic contractile unit of muscle tissues, allowing for movement of the body. Kinases are enzymes that transfer high-energy phosphate groups to substrates, fueling metabolism.
Patterns of Expression The human genome, if laid out flat would be one meter long, and codes for over 20,000 genes. A cell roughly measures 0.0001 meter wide. Highly refined mechanisms modulating gene expression allow for such a vast amount of information to be packed tightly into a single cell with order. Each cell expresses specific genes, like a fine dining restaurant, an impressive array of dishes emerge from one kitchen. From one embryo, complex organs and tissues develop to become an organism capable of metabolizing food and converting light into neurological signals.
DNA is stored in a highly condensed form inside the nucleus. It is wrapped around proteins called histones like yo-yos, which further coil to form a densely packed rope-like structure called chromatin. This chromatin condenses into a chromosome - a dense single unit of DNA. When DNA is tightly packed into chromatin, it is not accessible by RNA Polymerase to be transcribed. Genes are turned “off and on” selectively. As books are organized in library shelves, you take a book off the shelf and open it when you need to find a piece of information. For transcription factors to access target sequences activating transcription, the chromatin structure needs to be relaxed, exposing the DNA sequence to activating proteins.
Epigenetics is the study of gene expression modification that does not involve alterations to the DNA sequence. There are two main categories of epigenetic regulation: histone modification and DNA methylation.
Enzymes modify histone proteins by adding or removing small molecules. Epigenetic modifications of histones are phosphorylation, methylation, ubiquination, and acetylation. These modifications directly affect the degree of tightness of chromatin, disrupt the binding of proteins to DNA bound as chromatin, and can attract proteins to chromatin. Histone modification results in facilitation or inhibition of gene expression (Gibney).
A chromosome unwound to display the histones wrapped in DNA
Cytosine, a nucleotide base of DNA, can be modified through methylation. The addition of a methyl group to the backbone of DNA results in a shift in biophysical characteristics, changing how proteins interact with the DNA molecule. Methylation is generally associated with gene repression, and patterns of DNA methylation on specific genome locations have been associated with developmental outcomes (Chater-Diehl).
Epigenetic mechanisms have been shown to regulate complex outcomes such as physical appearance, metabolism, behavior, and longevity. These patterns are also not static, environmental and behavior inputs will influence epigenetic patterns in an organism over time. Stimuli such as oxygen availability, sunlight, radiation, diet, and trauma can trigger epigenetic adaptations (Liberman). A multitude of physiological and psychological possibilities exist from one genetic code.
Patterns of histone modification and DNA methylation can be copied during cellular replication, meaning physical patterns of gene expression can be transgenerationally inherited. Plasticity in gene expression confers an organism with the ability to adapt to changing environmental stimuli, but has broad implications for developmental patterns of offspring. Studies have described links between the nutritional status of parents and epigenetic programming in offspring, suggesting inherited epigenetic patterns play a role in childhood obesity (Panera). Shifts in histone modification patterns correlated with a decrease in expression of pro-inflammatory genes has been observed among meditation practitioners, even after a short period of sustained practice (Kaliman).
Daily practices, nourishment, our relationships, and lived experiences have profound impacts at the molecular level, influencing the expression of being within every cell in the body.
RECOMMENDED READINGThe Song of the Cell Siddartha Mukherjee
The Immortal Life of Henrietta Lacks Rebecca Skloot
The Selfish Gene Richard Dawkins
The Epigenetics Revolution: How Modern Biology is Rewriting our Understanding of Genetics, Disease, and Inheritance Nessa Carey
Rainbow and the Worm Mae-Wan Ho
Body Electric, Robert Becker & Gary Selden
Rosalind Franklin, The Dark Lady of DNA Brenda Maddox
The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race Walter Isaacson
Silent Spring Rachel Carson
Surely You’re Joking, Mr. Feynman! Richard P. Feynman
BIBLIOGRAPHYAlberts B, Johnson A, Lewis J, et al. The Cell. New York: Garland Science; 2002.
Chater-Diehl E, Goodman SJ, Cytrynbaum C, Turinsky AL, Choufani S, Weksberg R. Anatomy of DNA methylation signatures: Emerging insights and applications. Am J Hum Genet. 2021 Aug 5;108(8):1359-1366.
Chen, FL., Yin, HY. & Tang, Y. PROK2–PROKR2 Signaling: New Contributor to Pleasant Touch. Neurosci. Bull. 39, 356–358 (2023).
Gibney ER, Nolan CM. Epigenetics and gene expression. Heredity. 2010;105:4–13.
Kaliman P, Alvarez-López MJ, Cosín-Tomás M, Rosenkranz MA, Lutz A, Davidson RJ. Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology. 2014 Feb;40:96-107
Liberman N, Wang SY, Greer EL. Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms. Curr Opin Neurobiol. 2019 Dec;59:189-206. doi:
Liu B, Qiao L, Liu K, Liu J, Piccinni-Ash TJ, Chen ZF. Molecular and neural basis of pleasant touch sensation. Science. 2022 Apr 29;376(6592):483-491.
Panera N, Mandato C, Crudele A, Bertrando S, Vajro P, Alisi A. Genetics, epigenetics and transgenerational transmission of obesity in children. Front Endocrinol (Lausanne). 2022 Nov 14;13:1006008.
Phillips, T. (2008) Regulation of transcription and gene expression in eukaryotes. Nature Education 1(1):199
Rohr S. Role of gap junctions in the propagation of the cardiac action potential. Cardiovasc Res. 2004 May 1;62(2):309-22.
