Histology, Cell

Structure

Each cell is enclosed by a delicate plasma membrane that separates its internal contents from the external environment. Within the cell, the protoplasm consists of both the cytoplasm and the nucleus (see Image. Ring Sideroblasts). The cytoplasm is composed of the cytosol, also known as hyaloplasm, and various organelles. The cell membrane functions as a selective barrier that maintains cellular integrity.

Just as the human body relies on specialized organs and tissues to function properly, cells contain distinct components called "organelles," each responsible for a specific function essential to cellular survival. Examples of these organelles include the Golgi apparatus (or Golgi bodies), mitochondria, ribosomes, lysosomes, and the endoplasmic reticulum.[4] The cytoplasm also houses small, nonliving structures known as cell inclusions, which contain substances such as melanin, glycogen, and enzymes that contribute to various cellular processes.

Although the cytosol within the cytoplasm is watery, the cytoplasm itself has a gel-like consistency due to the presence of organelles. The cytoskeleton is composed of microfilaments, microtubules, and intermediate filaments embedded within the cytosol. This structural network not only gives the cell its shape but also helps maintain its stability and organization.[5]

Function

Types of Cells

Cells are of different types, each with a unique function. Estimates suggest that the adult human body contains over 200 different cell types.

Stem cells serve as the foundation from which all other cells originate. These cells exist in different forms, each specialized for producing specific cell types.[6] Muscle cells include 3 primary categories: skeletal, smooth, and cardiac, each contributing to movement and contraction in different parts of the body. Bone cells comprise osteocytes, osteoclasts, and osteoblasts, which work together to maintain bone structure and function.

Cartilage cells contribute to cartilage formation and maintenance. These cells are classified into chondrocytes, chondroblasts, and chondroclasts. Blood cells encompass a variety of types, including platelets and red (RBCs) and white (WBCs) blood cells, such as neutrophils and basophils. Blood cells are critical to oxygen and nutrient delivery, immunity, and tissue repair.

Sex cells, which include sperm and ova, progress through multiple developmental stages. In the male body, primordial cells give rise to primary and secondary spermatocytes, which mature into spermatids and, ultimately, into sperm. Additional supporting cells, such as Sertoli cells, provide structural and nutritional support, while Leydig cells produce hormones essential for reproductive function.

Nervous system cells, including neurons, oligodendrocytes, astrocytes, and microglia, facilitate communication and support within the nervous system.[7] Fat cells, also called "lipocytes," store energy and provide insulation.

General Cell Functions

Cells perform a wide range of functions, each essential to maintaining life and ensuring the seamless progression of physiological processes. Cells contribute to body structure by maintaining the specific shape and form of different tissues and organs. Growth occurs through cell division, with stem cells giving rise to new cell types. During childhood, rapid increases in cell size and number occur, but this process slows upon reaching adulthood. Growth is regulated by genes that vary across organs and tissues.[8]

Apoptosis refers to the self-digestion and removal of dead or worn-out cells.[9] This process is essential for remodeling, morphogenesis, and tissue regeneration. Abnormally high rates of apoptosis occur in degenerative diseases, while insufficient apoptosis is characteristic of cancer cells.[10] Metabolism supports cell growth and proliferation through the synthesis of proteins, carbohydrates, and lipids.[11]

Temperature regulation is closely linked to metabolism, as mitochondria generate energy necessary for cellular and bodily functions. Energy production also leads to increased temperature. Intercellular communication is not a unique function of neurons within the nervous system, as it also occurs between other cells, enabled by substances that include enzymes, hormones, amino acid derivatives, and ions, to name a few. Cells remain in constant interaction to support metabolism, growth, development, division, and transport.[12]

The plasma membrane regulates the transportation of substances in and out of the cell, demonstrating selective permeability. Transport can be active or passive, allowing the movement of essential elements such as water, carbon dioxide, oxygen, and glucose. Reproduction occurs through cell division and multiplication, which take place in most cells of the body. The union of male and female gametes forms a zygote, marking the beginning of a new life (see Image. Fertilization of the Ovum).

The Cell Cycle

The cell cycle consists of a series of repetitive changes within a cell, ultimately leading to the production of daughter cells. While most cells undergo division and replication, their cell cycle patterns vary. Some cells, such as stem cells, divide continuously throughout life. Others, like neurons, divide only during early development and cease replication even when damaged. Some, like liver cells, divide only when necessary.[13]

Cells divide through 2 primary methods: mitosis and meiosis. Mitosis occurs in somatic cells and is essential for growth and the replacement of dead or damaged cells. This process results in 2 daughter cells that are exact replicas of the parent cell. Meiosis, on the other hand, takes place in germ cells, specifically in sperm and ova. Unlike mitosis, meiosis produces daughter cells that are genetically unique rather than identical copies of the mother cell.

Mitosis, also referred to as the "M stage," consists of 4 phases. Prophase is marked by chromatin condensation and the disappearance of the nuclear membrane. Metaphase follows, during which chromosomes align at the cell's equatorial plane. In anaphase, sister chromatids separate and move toward opposite poles. Finally, telophase involves the reformation of the nuclear membrane around each set of chromosomes, completing the division process.[14]

The interphase is the period between 2 mitotic divisions, subdivided into 3 stages: G1, S, and G2. During G1 (1st gap), the cell grows and produces essential proteins. The S (synthesis) phase is characterized by DNA replication, ensuring that genetic material is duplicated for the next division. In G2 (2nd gap), the cell prepares for mitosis by making proteins required for cell division.[15]

Meiosis consists of 2 sequential divisions. The 1st meiotic division is lengthy and occurs in 4 stages. Leptotene is the initial phase, where chromosomes begin to condense. In zygotene, homologous chromosomes pair up, forming synapses. Pachytene follows, during which genetic recombination occurs, increasing genetic diversity. Diplotene is marked by the separation of homologous chromosomes while remaining connected at crossover points.[16]

The 2nd meiotic division closely resembles mitosis, with 2 key differences. The DNA content is reduced by half, and the daughter cells produced are not identical to the parent cell. This reduction is essential for maintaining the chromosome number across generations and ensuring genetic variation.

Tissue Preparation

Cells may be observed in a viable state by growing them in a controlled culture, allowing for microscopic study. This process is referred to as "in vitro," a Latin term meaning "in glass." Under these conditions, cells continue to grow as continuous cell lines and maintain functional cohesion similar to their behavior within the body.

Cells isolated from their natural environment lose their structure and function, revealing little about their actual arrangement in healthy or diseased states. To preserve their structural integrity, researchers prepare thin sections along with surrounding tissue, making them suitable for examination under light and electron microscopes. These sections are labeled with tracer materials to track changes over time. Due to their fragility, the sections require mounting on glass slides for secure handling.

For light microscopy, tissue sections undergo preparation using the paraffin technique, which involves 8 sequential steps. Tissue sampling entails obtaining a specimen through surgical excision or biopsy. All unwanted connective tissue and structures must be carefully removed using sharp instruments to avoid distortion. The sample should not exceed 1 cm in size to ensure proper fixation. Tissue fixation follows immediately after dissection to preserve the specimen. This process hardens the soft tissue and prevents postmortem degradation. Formalin is commonly used as a fixative in light microscopy, providing benefits such as improved staining, elimination of pathogenic microorganisms for safe handling, and inhibition of cellular hydrolytic enzymes.[17]

Dehydration occurs by immersing the tissue in a series of increasing alcohol concentrations until it reaches absolute alcohol.[18] Once dehydrated, the sample undergoes clearing, where alcohol is removed by soaking the tissue in xylol. This step prepares the tissue for embedding, where it is passed through warm paraffin, replacing the xylol and filling all spaces previously occupied by water. The paraffin hardens as it cools, stabilizing the sample for sectioning.

In the sectioning stage, the embedded tissue is sliced into thin sections using a microtome, producing delicate slices ranging from 1 to 9 μm. Light microscopy typically requires sections between 4 and 8 μm thick. If thinner sections are necessary, plastic or epoxy resin is used instead of paraffin wax.

The final steps involve mounting and staining the tissue for microscopic examination. The thin sections are mounted on glass slides and treated with xylol to remove residual paraffin wax. The sections are then rehydrated by passing through decreasing concentrations of alcohol and rinsed with water. The prepared slides are stained with hematoxylin and eosin (H&E) to enhance cellular detail, making the tissue structure visible under the microscope.[19]

Histochemistry and Cytochemistry

Cytochemistry involves the analysis, visualization, and identification of the microanatomical locations of biochemical content and its surrounding environment within a cell. This visualization is performed on histological sections using electron microscopy or biochemical analyses. Various sophisticated methods facilitate cytochemical studies, including enzyme cytochemistry, microincineration, microspectrophotometry, radioautography, cryo-techniques, x-ray microanalysis, and immunocytochemistry. These techniques provide detailed insights into the ultrastructure and organelles of cells.

Microincineration techniques help determine the distribution of mineral elements such as calcium, sodium, and potassium in cells, tissues, and organs. Enzyme cytochemistry localizes enzymes within a cell or tissue by catalyzing chromogenic substrates that produce visible staining. This method relies on enzymatic colorimetric reactions to identify specific cellular components. Microspectrophotometry measures the spectra of intracellular organelles by analyzing their interaction with electromagnetic radiation at various wavelengths. Organelles and ultrastructures become visible due to their differential responses to this radiation.

Radiography and x-ray techniques reveal the spatial distribution of radioactively labeled isotopes within cells and tissues. Immunocytochemistry utilizes labeled antibodies to detect specific proteins or antigens, allowing precise visualization of anatomical structures based on antibody-antigen interactions.

Cytochemistry enables the detection and identification of biochemical components within a cell, contributing to a better understanding of cellular function. This field has provided valuable insights into the physiological, pathological, and experimental conditions affecting both cells and tissues.

Histochemistry focuses on identifying and mapping the distribution of chemical components within and between cells. This field combines histological and biochemical techniques, such as specialized stains and indicators, to analyze the chemical composition of cells and tissues. Light and electron microscopy play a crucial role in visualizing biological structures, making histochemistry essential for studying cellular organization.

Histochemical methods contribute to understanding the molecular basis of various pathologies, particularly cancer progression. Technological advances have enabled live-cell staining using fluorescent dyes, including intrinsic fluorophores, genetically encoded fluorophores, self-labeling systems, and ligase-based tag systems. These innovations have expanded the applications of histochemical analysis to living cells, enhancing its value in research.

Histochemistry has also advanced the study of hard tissues, such as odontoblasts, leading to therapeutic approaches for dentin mineralization.[20] Immunohistochemistry, a specialized branch of histochemistry, aids in understanding nerve cell differentiation during development.[21] Additionally, histochemical techniques support regenerative and reparative medicine by providing insights into tissue repair mechanisms. These methods are frequently employed in diagnosing metabolic disorders and various disease pathologies, further demonstrating their clinical significance.

Microscopy, Light

Examining cells under a light microscope reveals their structure and organelles. However, finer details become apparent only when viewed with a more advanced electron microscope.

Cytoplasm

The cytoplasm (derived from the Greek "kytos," meaning covering) is also referred to as plasma (from the Greek "plasma," meaning molded), as it appears to surround the nucleus. This region of the cell is densely packed with 2 broad categories of components: cytoplasmic organelles and macromolecules. Cytoplasmic organelles, often described as minute organs, are suspended within the cytoplasmic matrix, also known as the cytosol. In addition to these essential structures, the cytoplasm contains nonessential elements known as inclusion bodies, which may contain pigmented granules or stored fat droplets (see Image. Human Herpes Virus 6 Cellular Infectio)n.[22]

Nucleus

The nucleus is the most rigid and largest organelle in the cell, typically occupying its central portion.[23] The name of this organelle comes from its resemblance to a nut within a shell (derived from the Latin "nux" and Greek "karyo," both meaning nut). The nucleus is the cell's control center, often referred to as its “brain.” Surrounding this structure is a double-layered, thin membrane known as the nuclear envelope, which contains numerous perforations called "nuclear pores." These specialized pores are crucial for selective permeability, regulating the exchange of macromolecules between the nucleus and cytoplasm.[24]

At the center of the nucleus, one or more small, nonmembranous bodies called "nucleoli" are present. The nucleolus is composed of RNA and is vital to ribosome formation. The nucleus exhibits a heterogeneous structure with electron-dense (dark) and electron-lucent (light) regions. The dense areas, called "heterochromatin," consist of tightly coiled inactive chromatin and often form irregular clumps near the nuclear periphery. The lighter, electron-lucent material, termed "euchromatin," represents active DNA involved in RNA synthesis. Together, heterochromatin and euchromatin form "chromatin," derived from the Greek word "chroma," meaning color, due to its affinity for certain dyes.

In a nondividing state, DNA molecules appear as granules or thread-like chromatin (see Image. DNA Analysis). During cell division, DNA molecules condense into short, rod-like structures called "chromosomes." Human cells typically contain 46 chromosomes, except for mature sex cells, which have a haploid set of 23 chromosomes. DNA carries the genetic code that directs enzyme production and other cellular proteins, ultimately determining both cell structure and function. Suspended within the nucleus is a nonstaining component called the "nuclear sap," which houses the nucleoli.

Ribosomes

Ribosomes measure approximately 15 nm in diameter and exist in both attached and free, unbound forms. Many are tethered to the rough endoplasmic reticulum (rER), while others are dispersed throughout the cytoplasm. When found individually, these organelles are referred to as "monosomes," whereas groups of ribosomes are called "polyribosomes." Each ribosome consists of subunits made of RNA, which may be ribosomal (rRNA), messenger (mRNA), or transfer (tRNA) RNA. Ribosomes are responsible for synthesizing proteins used both inside and outside the cytoplasm, making them the cell’s protein factory. The role of these structures is to “translate” genetic instructions from DNA into functional proteins.[25]

Endoplasmic Reticulum

The endoplasmic reticulum is a network located toward the center of the cytoplasm and is considered one of the largest organelles. This complex structure consists of membrane channels made up of cisterns or tubules. The cytoplasm within these tubules is called "vacuoplasm," while the cytoplasm outside is referred to as "hyaloplasm" or "cytosol." The endoplasmic reticulum performs various functions, including protein synthesis, calcium storage, steroid synthesis, and lipid metabolism. The shape of the endoplasmic reticulum varies, with each form associated with a distinct function. Cells that synthesize large amounts of proteins tend to have more sheets, while those involved in lipid synthesis contain more tubules.[26]

The endoplasmic reticulum exists in 2 forms: rough and smooth. The rER is covered with ribosomes and plays a role in protein synthesis. The smooth endoplasmic reticulum (sER) is involved in the production of specific lipids and carbohydrates.

The rER has membranes with a rough outer surface due to the presence of ribosomes. This organelle functions as an internal transport system for the cell, facilitating the movement of synthesized proteins. The rER lumen is continuous with that of the smooth endoplasmic reticulum and the perinuclear space. This structure primarily modifies synthesized proteins used by the cell.

The sER consists of membranes with a smooth outer surface and lacks ribosomes. This organelle is responsible for lipid production and further processing of membrane proteins synthesized by the rER. The sER also aids in drug detoxification.

Only properly folded proteins are delivered to the Golgi apparatus for further processing. If a protein is defective or incompletely folded, it undergoes degradation within the endoplasmic reticulum. An excessive accumulation of misfolded proteins can result in a condition known as endoplasmic reticulum stress, which occurs when protein production surpasses the organelle’s capacity to manage and process them effectively.[27]

Golgi Apparatus

The Golgi apparatus consists of irregular bodies located near the nucleus. These structures become visible under a light microscope when stained with silver salts. When examined with an electron microscope, the Goldgi apparatus appears as a ribbon-like formation bound by a single-layered membrane. The Golgi apparatus resembles the sER, comprising stacks of cisternae and small, rounded vesicles at the periphery. The primary functions of this organelle include protein biosynthesis and packaging protein molecules for export from the cell. Materials from the endoplasmic reticulum reach the Golgi apparatus in vesicles. Functionally, the Golgi apparatus is divided into 3 regions: the cis-, trans-, and medial Golgi.

Lysosomes

Lysosomes are vesicles that pinch off from the Golgi apparatus. These structures contain enzymes that degrade and recycle cellular waste through a process known as autophagy. This mechanism eliminates unwanted molecules and foreign particles, such as bacteria and viruses, that enter the cell. Nearly 60 different lysosomal hydrolases, the chemicals responsible for this process, have been identified.[28] Thus, lysosomes are also called "digestive bags" or "cellular garbage disposal units."

In rare cases, these organelles may release their enzymes within the cell, leading to self-destruction. Consequently, lysosomes have also been described as "suicide bags." However, recent research has revealed that lysosomes are not merely waste-processing structures, but they also regulate energy metabolism and cellular clearance. Additionally, lysosomes contribute to plasma membrane repair, bone resorption, and immune responses.[29][30]

Mitochondria

Mitochondria appear as rod-shaped or granular structures, giving them their name, which derives from "mitos"(granules) and "chondrium" (rod). Mitochondria are often referred to as the "power source" of the cell because they generate the energy required for cellular functions, including movement, division, contraction, and secretion. This energy production occurs through the breakdown of food, leading to the formation of adenosine triphosphate (ATP), the primary fuel for energy-dependent processes.

Mitochondrial length ranges from 0.5 to 2 μm, and the number varies depending on the metabolic activity of the cell. Metabolically active cells contain more mitochondria, while less active cells have fewer. Each mitochondrion consists of an outer and an inner membrane. The inner membrane features numerous folds called "cristae." Within the inner membrane lies the matrix, a granular material containing essential enzymes for ATP production. Mitochondria serve as the site of cellular respiration, the process responsible for energy generation.[31]

Vesicles and Vacuoles

Vesicles and vacuoles function as storage compartments within the cell. These structures hold proteins, waste materials, and nutrients. In plant cells, vacuoles store water, contributing to structural support and maintaining cellular pressure.[32]

Centrioles and Centrosomes

Centrioles and centrosomes are crucial for cell division and replication. These structures help organize microtubules and facilitate the proper distribution of chromosomes during mitosis.[33]

Cell Membrane

The cell membrane, also known as the plasma membrane or plasmalemma, derives its name from the Greek word "lemma," which means bark. This trilaminar structure is composed primarily of lipids, including phospholipids, cholesterol, and glycolipids. Cell membrane proteins include integral membrane proteins, peripheral membrane proteins, and glycoproteins. A small amount of carbohydrates is also present in this protective barrier.

The cell membrane measures only 7.5 nm. Consequently, this structure may be observed only under an electron microscope. The cell membrane serves as a barrier that holds the cell together, separates it from the surrounding environment, and maintains its shape. Membrane rupture results in the release of cellular contents.

The membrane exhibits selective permeability, allowing oxygen and water to pass freely while restricting the movement of sodium and potassium ions. Large molecules enter the cell through endocytosis. Some cells specialize in engulfing foreign materials through phagocytosis, while others take in small fluid molecules through pinocytosis. The membrane also contains specific receptors for enzymes and hormones, facilitating cellular communication and function. Certain cells feature surface projections such as cilia, flagella, or microvilli, which aid in movement, absorption, or other specialized functions, such as sensory reception.[34]

Pathophysiology

Oxygen, as a biradical, reacts with various metal ions and biological molecules in a process known as oxidation. Mitochondrial respiration generates reactive oxygen species (ROS) such as superoxide anion radical (O2·?), hydrogen peroxide (H2O2), and hydroxyl radical (·OH). All biological molecules, including DNA, are vulnerable to oxidative damage. To counteract oxidation-induced stress, the body employs antioxidant mechanisms involving superoxide dismutases, peroxidases, peroxiredoxins, glutathione, and glutaredoxins.

DNA constantly sustains damage from cellular metabolites and external mutagens, which can cause strand breakage during replication. Cyclin-dependent kinases (CDKs), which regulate the cell cycle, also contribute to DNA repair.[35] Double-stranded breaks are the most toxic DNA lesions. If left uncorrected or incorrectly repaired, these breaks may result in loss of heterozygosity or extensive chromosomal rearrangements. Other types of DNA damage include single-stranded breaks, depurination, depyrimidination, O6-methylguanine formation, and cytosine deamination. These alterations may lead to disease if not corrected by the DNA repair system.

The DNA repair system includes nonhomologous DNA end joining (NHEJ), base excision repair (BER), single-strand break repair (SSBR), homologous recombination, and interstrand cross-link (ICL) repair. Defects in homologous recombination and ICL repair can contribute to Fanconi anemia, familial breast cancer, and ovarian cancers. Insufficient NHEJ function is associated with severe combined immunodeficiency. Pathologies linked to BER and SSBR deficiencies include hyper-immunoglobulin M syndrome and colorectal carcinomas. Defective SSBR also manifests with ataxias. DNA damage response pathways are crucial for maintaining genome stability, preventing neurodegeneration and malignant transformation, and supporting normal growth, immune development, and neurogenesis.[36]

Cellular Adaptations

Cells undergo various adaptations in response to external stimuli or environmental demands. These changes can be physiological or pathological and sometimes contribute to disease progression. Cellular adaptations generally fall into 5 categories.

Hypertrophy refers to an increase in cell size without an increase in cell number, leading to an overall enlargement of a structure. This adaptation is evident in the pregnant uterus and in the muscles of bodybuilders. The increase in muscle mass is attributed to a protein growth factor called "insulin-like growth factor 1" (IGF-1).[37]

Hyperplasia involves a rapid increase in cell number, resulting in an overall enlargement of a tissue or organ. This process can be physiological or pathological. A physiological example is the expansion of the pregnant uterus. Pathologically, hyperplasia may be either benign or malignant. Benign prostatic hyperplasia (BPH) is a common example of benign hyperplasia. In contrast, endometrial hyperplasia, which can be a precursor to endometrial carcinoma, is a pathological condition characterized by excessive proliferation of the endometrial glandular tissue and stroma.[38]

Atrophy is the opposite of hypertrophy, and it involves a reduction in cell size that leads to a decrease in the overall size of a tissue or organ. A classic example of physiological atrophy is the shrinkage of the thymus after middle adulthood. Disuse atrophy occurs when a specific tissue or organ diminishes in size due to prolonged inactivity. The process results from a loss of cell organelles, proteins, and cytoplasm.[39]

Metaplasia is an adaptive response in which one type of healthy cell is replaced by another within a tissue or organ. This change occurs in response to an abnormal stimulus.[40] A common example is the transformation of cells in the lower esophagus due to chronic gastroesophageal reflux, giving rise to a condition known as Barrett esophagus.

Dysplasia refers to the abnormal arrangement of cells caused by alterations in their typical growth patterns. This condition often represents a precancerous change, increasing the risk of progression to malignancy if left untreated.[41]

Clinical Significance

Disruptions in cellular function, whether due to genetic mutations, structural defects, or environmental factors, contribute to numerous pathological conditions. Studying these aberrations helps diagnose diseases, develop targeted therapies, and understand the progression of disorders affecting multiple organ systems.

Mitochondrial Cytopathy Syndromes

Mitochondrial cytopathy syndromes result from abnormalities in mitochondrial DNA, which interfere with mitochondrial function and, consequently, cellular processes. These syndromes result from either mutations of nuclear DNA or maternally inherited mitochondrial genomes. Symptoms vary widely but often include muscle weakness, elevated lactic acid levels, and degenerative brain lesions. Diagnosis involves examining muscle cell biopsies under an electron microscope, where paracrystalline mitochondrial inclusions are characteristic. Additional investigations include measuring serum and cerebrospinal fluid lactate levels and conducting neuroradiological tests.

Researchers have identified nearly 200 types of mitochondrial DNA mutations, with ongoing advancements leading to the detection of new variants.[42] Dysfunctional or mutated mitochondria have also been implicated in malignant transformations of hematopoietic stem cells, contributing to leukemia.[43]

Golgi Apparatus Defects

Structural and functional defects of the Golgi apparatus play a significant role in various cardiovascular diseases, including heart failure, cardiomegaly, and arrhythmias. While Golgi body dysfunction occurs in multiple conditions, its impact is most pronounced in cardiovascular conditions, given this organelle’s essential role in protein transport, biosynthesis, and distribution within the cardiovascular system.[44]

Cell Membrane Defects

Cell membrane defects may involve RBCs when inherited mutations alter membrane structure, leading to a shortened RBC lifespan and premature removal from circulation. These abnormalities manifest in heritable conditions such as hereditary spherocytosis, stomatocytosis, ovalocytosis, and elliptocytosis.[45] Similar defects occur in muscular dystrophies, where mutations disrupt proteins embedded in cell membranes. Disorders such as dystrophinopathy, Bethlem myopathy, merosinopathy, dysferlinopathy, sarcoglycanopathies, and caveolinopathy arise from these protein errors, often leading to abnormal ion flux that contributes to muscle cell degeneration.[46]

Membrane defects are also implicated in receptor-related disorders like Graves disease, certain types of diabetes and obesity, and multiple sclerosis. Changes in lipid composition, as seen in multiple sclerosis and muscular dystrophy, further disrupt membrane function. Abnormal membrane permeability plays a role in cystic fibrosis, bacterial toxin-related conditions, and diseases linked to specific transport alterations. Additionally, cytoskeleton-membrane defects, such as those in Chediak-Higashi disease, further illustrate the diverse clinical impact of membrane dysfunction.[47]

Lysosome Storage Diseases

Lysosomes contain more than 50 different types of membrane proteins, and abnormalities or dysfunction in some of these proteins have been linked to nearly 50 distinct lysosomal storage diseases. Mutations in lysosomal genes predispose individuals to a range of conditions, including obesity, infections, cancer, and neurodegenerative disorders, such as Parkinson, Gaucher, and Alzheimer diseases.

Nuclear Defects

Mutations affecting nuclear structure and composition contribute to various conditions, including muscular dystrophy, cancer, aging, and cardiomyopathies.[48] Neurodegenerative disorders are often characterized by the accumulation of pathogenic intranuclear protein aggregates, which form intranuclear inclusion bodies.[49]

Endoplasmic Reticulum Abnormalities

Anomalies in endoplasmic reticulum-shaping proteins have been implicated in diseases such as hereditary spastic paraplegia and Alzheimer disease. Prolonged endoplasmic reticulum stress is associated with type 2 diabetes, neurodegeneration, liver disease, atherosclerosis, and several forms of cancer.

Cytoplasmic Errors

Maintaining an appropriate cellular composition is essential for proper function. Excess cytoplasm has been linked to defects in chromosome alignment, spindle pole morphology, and checkpoint signaling, all of which contribute to chromosome segregation errors.[50]

DNA Mutation

Mitotic errors can result from prolonged exposure to radiation, particularly nuclear radiation, as well as certain chemicals and drugs. However, some cells, such as neural and cardiac cells, do not undergo mitosis and instead remain in the Go phase.[51]

Tumors

The rate of cell division varies significantly across different cell types, with epithelial cells exposed to friction undergoing the most rapid turnover. Cell division correlates with physiological demand, but excessive and uncontrolled proliferation can result in tumor formation.[52]