Cell Structure, Membrane Dynamics, and Transport Mechanisms

Foundations of Cell Biology and Structural Principles

• Principles of Cell Theory

  • All living organisms are composed of one or more cells.

  • Cells are the smallest and most fundamental living units of life.

  • Cells arise exclusively from the division of pre-existing cells, establishing that all modern cells represent an unbroken line of evolutionary descent from the first ancestral living cells.

• Physical Factors Limiting Cell Size

  • Most cells are microscopic because they rely on passive diffusion for the movement of nutrients, gases, and waste products into and out of the cellular environment.

  • Diffusion Rates: The efficiency and rate of diffusion are governed by four primary variables: surface area available for transport, temperature, magnitude of the concentration gradient, and diffusion distance.

  • Surface Area-to-Volume Ratio Constraints: As a cell increases in linear dimension, its volume grows proportionally to the cube of its radius ($V \propto r^3$), whereas its surface area increases only as the square of its radius ($SA \propto r^2$). Consequently, larger cells suffer a dramatic reduction in surface area relative to volume, rendering plasma membrane transport insufficient to supply internal metabolic demands.

  • Structural Strategies: To overcome volume-driven diffusion limits, organisms must remain multicellular with small individual cells or adopt elongated, flattened, or non-spherical cell morphologies that maximize surface-area-to-volume ratios.

• Universal Structural Features of All Living Cells

  • Genetic Material Storage Area: A nucleoid region in prokaryotes or a membrane-enclosed nucleus in eukaryotes houses the genomic DNA.

  • Cytoplasm: A semifluid internal matrix (cytosol) containing solutes, metabolic machinery, and cellular structures.

  • Ribosomes: Macromolecular complexes comprised of ribosomal RNA (rRNA) and proteins that execute protein synthesis across all domains of life.

  • Plasma Membrane: A dynamic phospholipid bilayer that isolates the internal cellular environment from external surroundings.

• Prokaryotic Versus Eukaryotic Cell Architecture

  • Prokaryotic Domain Features (Archaea and Bacteria):

  • Structural simplicity; lack a membrane-bound nucleus and internal membrane-bound organelles.

  • Genomic DNA exists as a single circular chromosome localized in the nucleoid.

  • Enclosed by a rigid cell wall positioned external to the plasma membrane.

  • Eukaryotic Domain Features:

  • High structural complexity characterized by extensive internal compartmentalization via an endomembrane system and membrane-bound organelles.

  • Genomic DNA is organized into multiple linear chromosomes situated within a double-membrane bound nucleus.

  • Supported by an internal cytoskeletal network that regulates shape, spatial organization, and intracellular trafficking.

  • Plant and animal eukaryotic lineages share core organelles (plasma membrane, nucleus, ribosomes, mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes), but plant cells uniquely possess a cellulosic cell wall, chloroplasts for energy capture, and a large central vacuole for turgor regulation.

Molecular Organization of Biological Membranes

• The Four Core Components of Cellular Membranes

  • Phospholipid Bilayer: Forms a flexible, self-sealing matrix that acts as a primary permeability barrier between intracellular and extracellular compartments.

  • Transmembrane Proteins: Integral membrane proteins that span the entire lipid bilayer to conduct active or passive transport, enzymatic reactions, and signal transduction.

  • Interior Protein Network: Peripheral or intracellular proteins (such as spectrins and clathrins) anchored to the inner leaflet or cytoskeleton that dictate cell shape and organize coated pits.

  • Cell-Surface Markers: Extracellular carbohydrate chains covalently bound to lipids (glycolipids) or proteins (glycoproteins) that function in tissue identity and immune recognition.

• Phospholipid Structure and Bilayer Dynamics

  • Amphipathic Molecular Structure: A single phospholipid molecule consists of a three-carbon glycerol backbone attached to two nonpolar hydrophobic fatty acid tails and a polar hydrophilic phosphate head group (often linked to an organic molecule such as choline).

• Spontaneous Assembly: Due to the hydrophobic effect, phospholipids spontaneously arrange in aqueous environments into a bilayer where nonpolar hydrocarbon tails sequester inward away from water, while polar heads face the aqueous cytosol and extracellular fluid.

• Fatty Acid Saturation: Saturated fatty acid tails contain no carbon-carbon double bonds ($C=C$), allowing straight chains to pack tightly, reducing fluidity. Unsaturated fatty acid tails contain one or more cis-$C=C$ double bonds, creating kinks that disrupt packing and increase membrane fluidity.

• Lipid Diversity: Eukaryotic cells possess over 1000 distinct lipid species divided into three primary structural classes: glycerol phospholipids, sphingolipids, and sterols (e.g., cholesterol).

  • Factors Governing Membrane Fluidity and Architectural Heterogeneity

• Temperature Adaptations: Cold environments compact lipid tails and reduce fluidity; bacteria compensate by utilizing fatty acid desaturase enzymes to introduce double bonds into membrane lipids.

• Organellar Membrane Differences: The lipid composition, thickness, and packing vary across endomembrane compartments:

  • Endoplasmic Reticulum (ER) Membranes: Comparatively thin, enriched in unsaturated fatty acids, exhibit major packing defects, and accommodate transmembrane domains (TMDs) approximately 20 amino acids long.

  • Plasma Membranes: Comparatively thick, enriched in saturated fatty acids and cholesterol, exhibit minor packing defects, possess anionic head groups on the inner leaflet, and accommodate TMDs averaging 25 amino acids long.

• The Fluid Mosaic Model: Biological membranes act as two-dimensional liquids in which integral proteins, lipids, and peripheral complexes dynamically drift laterally through the phospholipid matrix like floating objects on water.

  • Structural Classes and Motifs of Membrane Proteins

• Functional Diversity: Membrane proteins execute specialized roles classified into six major categories: Transporters, Enzymes, Cell-Surface Receptors, Cell-Surface Identity Markers, Cell-to-Cell Adhesion Proteins, and Attachments to the Cytoskeleton.

• Lipid-Anchored Proteins: Peripheral proteins modified with nonpolar lipid groups that insert directly into the hydrophobic core of the bilayer, anchoring the protein to the surface via direct chemical bonding domains.

• Transmembrane Domains (TMDs): Membrane-spanning protein segments composed predominantly of nonpolar, hydrophobic amino acids arranged in hydrophobic $\alpha$-helices. While a single $\alpha$-helix can anchor a protein, many receptors and transporters contain multiple hydrophobic $\alpha$-helices traversing the membrane.

• G-Protein-Coupled Receptors (GPCRs): A prominent superfamily of cell-surface receptors defined by seven transmembrane $\alpha$-helical domains. Encoded by roughly 800 genes in the human genome, GPCRs serve as targets for approximately one-third of all approved pharmaceutical drugs. Major family members include V2R (vasopressin 2 receptor), serotonin, adrenaline, opioid, cannabinoid, histamine, acetylcholine receptors, and rhodopsin.

• Pores and $\beta$-Barrels: Extensive nonpolar transmembrane regions can fold into a closed cylindrical sheet of $\beta$-pleated strands called a $\beta$-barrel. The exterior interacting with fatty acid tails is nonpolar, whereas the interior lumen is hydrophilic, creating open pores that allow water and small polar molecules to diffuse across the bilayer.

Membrane Dynamics and Transmembrane Transport Mechanisms

• Permeability Characteristics of the Phospholipid Bilayer

  • Hydrophobic Core Barrier: The nonpolar interior of the lipid bilayer acts as a barrier to most polar and charged substances.

  • Permeable Substances: Small, nonpolar, uncharged molecules with a molecular weight less than 500 grams per mole ($MW < 500\,\text{g/mol}$)—such as oxygen ($O_2$) and carbon dioxide ($CO_2$)—passively diffuse through the membrane down their concentration gradients.

  • Impermeable / Limited Permeability Substances: Hydrophilic polar molecules (e.g., glucose) and charged ions (e.g., $Na^+$, $K^+$, $Ca^{2+}$, $Cl^-$) exhibit minimal or zero passive permeability and require specialized transmembrane transport proteins.

• Passive Transport: Diffusion and Facilitated Transport

  • Simple Diffusion: The net movement of dissolved solute particles from a region of higher concentration to a region of lower concentration driven by random thermal motion, occurring without cellular energy consumption until dynamic equilibrium is established throughout the volume.

  • Facilitated Diffusion: Passive, protein-mediated transport of substances down their concentration gradients across a selectively permeable membrane.

  • Channel Proteins: Transmembrane proteins that create open hydrophilic passages across the hydrophobic core:

  • Ion Channels: Allow specific inorganic ions to move down electrochemical gradients.

  • Gated Channels: Channel proteins that open or close in response to specific chemical signals (ligands) or electrical potential changes (voltage).

  • Directional Factors: Ion flux through gated channels is dictated by relative concentration gradients, voltage differences across the membrane, and the open/closed state of the gate.

  • Carrier Proteins: Transmembrane proteins that bind specifically to the solute molecule they transport, undergoing a series of conformational changes to move the substrate across the bilayer. Carrier transport is passive (down-gradient) but exhibits saturation kinetics, where the maximum transport rate ($V_{\max}$) is limited by the total number of available carrier proteins.

• Osmosis, Osmotic Pressure, and Cellular Tonicity

  • Osmosis: The net movement or diffusion of water across a selectively permeable membrane toward a region of higher solute concentration (lower free water concentration).

  • Aquaporins: Specialized transmembrane protein channels that facilitate high-volume, rapid passage of water molecules across cell membranes.

  • Osmotic Concentration Terminology:

  • Isotonic Solution: Equal solute concentration relative to the cytoplasm; no net change in cell volume.

  • Hypertonic Solution: Higher solute concentration relative to the cytoplasm; causes water to diffuse out of the cell, resulting in cell shrinkage or plasmolysis.

  • Hypotonic Solution: Lower solute concentration relative to the cytoplasm; causes water to enter the cell, resulting in cell swelling.

  • Osmotic Pressure and Hydrostatic Balance: Osmotic pressure is defined as the external force required to completely halt osmotic water flow across a membrane.

  • Cells with Rigid Cell Walls (plants, fungi, prokaryotes, protists): Water influx builds internal hydrostatic pressure (turgor pressure) pushing outward against the cell wall until it balances osmotic pressure pushing inward, preventing cell rupture (yielding a normal turgid plant cell).

  • Animal Cells: Lacking cell walls, animal cells cannot withstand significant hydrostatic pressure; exposure to hypotonic environments causes unchecked swelling and osmotic lysis (bursting), requiring tight homeostatic control of isotonic extracellular fluids.

• Active Transport Systems

  • Definition: Protein-mediated movement of solutes across a membrane against their concentration gradient (from a region of low concentration to high concentration), requiring direct or indirect expenditure of cellular metabolic energy (ATP).

  • Carrier Protein Classifications:

  • Uniporters: Transport a single solute species in one direction.

  • Symporters: Transport two different solute species simultaneously in the same direction.

  • Antiporters: Transport two different solute species in opposite directions across the membrane.

• Primary Active Transport: The Sodium-Potassium ($Na^+/K^+$) ATPase Pump

  • Stoichiometry and Function: An integral membrane antiporter that hydrolyzes one molecule of ATP to export three sodium ions ($3\,\text{Na}^+$) out of the cell and import two potassium ions ($2\,\text{K}^+$) into the cytoplasm against their respective steep concentration gradients.

  • Step-by-Step Mechanism:

  1. Three intracellular $Na^+$ ions and one molecule of ATP bind to high-affinity binding sites on the cytoplasmic surface of the pump protein.

  2. Bound ATP undergoes enzymatic hydrolysis ($ATP + H_2O \rightarrow ADP + P_i$), transferring its terminal phosphate group directly to the pump protein (phosphorylation).

  3. Phosphorylation induces a major conformational change in the pump protein, closing the cytoplasmic gate, opening the extracellular gate, and reducing affinity for $Na^+$. The three $Na^+$ ions detach and diffuse into the extracellular fluid.

  4. The altered protein conformation exposes binding sites with high affinity for extracellular potassium ions ($K^+$). Two $K^+$ ions bind to these exposed sites.

  5. Binding of extracellular $K^+$ triggers dephosphorylation of the pump protein, releasing the inorganic phosphate ($P_i$) group.

  6. Dephosphorylation allows the protein to snap back to its original conformational shape, reducing its affinity for $K^+$. The two $K^+$ ions detach and diffuse into the cytoplasm. A new ATP molecule binds, re-initiating the cycle.

• Secondary Active Transport: Coupled Transport

  • Mechanism: Coupled transport utilizes ATP indirectly. Primary active pumps (like the $Na^+/K^+$ pump) spend ATP to establish a steep ion concentration gradient (e.g., high extracellular $Na^+$). As the ion diffuses down its gradient through a symporter or antiporter carrier protein, the released potential energy is harnessed to co-transport a second molecule (such as glucose or an amino acid) against its concentration gradient.

  • Glucose-$Na^+$ Symporter Example: Captures the downhill energy of $Na^+$ moving into the cytoplasm to pull glucose into the cell against a concentration gradient.

• Bulk Transport: Endocytosis and Exocytosis

  • Endocytosis: Energy-dependent uptake of bulk material or macromolecular substances into the cell via plasma membrane invagination and vesicle formation.

  • Phagocytosis: Uptake of large particulate matter, bacterial cells, or cellular debris ("cell eating").

  • Pinocytosis: Non-specific uptake of extracellular fluid containing dissolved solutes ("cell drinking").

  • Receptor-Mediated Endocytosis: Highly specific uptake process where target extracellular molecules (ligands) bind to localized transmembrane receptor proteins on the outer membrane leaflet. Bound receptors aggregate in coated pits lined on the cytoplasmic face by the structural protein clathrin. The pit invaginates to form an intracellular coated vesicle carrying the ligand (e.g., low-density lipoprotein / LDL uptake).

• Exocytosis: Energy-dependent secretion or export of bulk material out of the cell. Secretory vesicles derived from the Golgi apparatus fuse with the plasma membrane, discharging their internal contents into the extracellular space while adding new membrane lipids and proteins to the cell surface.

  • Plant Applications: Export of structural cell wall polysaccharides (cellulose, pectins).

  • Animal Applications: Secretion of peptide hormones, digestive enzymes, neurotransmitters, and extracellular vesicles (exosomes/microvesicles).

• Biomedical Application - Exosome Therapeutics: Exogenus Therapeutics and Lonza partnered to manufacture Exo-101, an exosome-based drug candidate derived from umbilical cord blood stem cells. Exo-101 delivers a cocktail of small RNAs, proteins, and anti-inflammatory lipids exhibiting regenerative, anti-inflammatory, and immunomodulatory properties, targeting clinical patient delivery in 2027.

The Endomembrane System and Cellular Organelles

• Compartmentalization via the Endomembrane System

  • The endomembrane system divides the eukaryotic cytoplasm into functional, membrane-bound compartments that isolate specific biochemical reactions and facilitate organized molecular transport.

• Components of the Endomembrane Pathway

  • Nucleus:

  • Enclosed by the nuclear envelope, composed of two distinct concentric phospholipid bilayers (four lipid layers total) perforated by nuclear pores that regulate macromolecular transport.

  • Contains genomic DNA organized into chromatin.

  • Houses the nucleolus, a specialized dense region responsible for ribosomal RNA (rRNA) transcription and ribosome assembly.

  • Ribosomes:

  • Non-membrane-bound complexes composed of rRNA and proteins found in all three biological domains.

  • Exist freely in the cytosol (synthesizing cytosolic proteins) or bound to the endoplasmic reticulum membrane (synthesizing membrane, organellar, or secreted proteins).

  • Endoplasmic Reticulum (ER):

  • Rough Endoplasmic Reticulum (RER): Studded with surface-bound ribosomes. Primary site for synthesized proteins destined for secretion, lysosomal targeting, or membrane insertion.

  • Smooth Endoplasmic Reticulum (SER): Lacks ribosomes. Functions in membrane lipid assembly, steroid synthesis, carbohydrate metabolism, drug detoxification, and intracellular calcium ($Ca^{2+}$) storage.

  • Golgi Apparatus:

  • Flattened stacks of membrane-bound sacs (Golgi bodies) organized into a receiving cis face (oriented toward the ER/nucleus) and a shipping trans face (oriented toward the plasma membrane).

  • Functions as the cell's molecular sorting, packaging, and modification center, attaching carbohydrate moieties to glycoproteins and lipids before dispatching them in transport vesicles.

  • Lysosomes:

  • Membrane-bound digestive vesicles arising from the trans face of the Golgi apparatus containing acid hydrolases.

  • Fuse with endocytic vesicles, phagosomes, or worn-out cellular organelles (autophagy) to break down proteins, nucleic acids, lipids, and carbohydrates into monomeric subunits for recycling.

  • Microbodies and Peroxisomes:

  • Enzyme-bearing metabolic vesicles that catalyze fatty acid oxidation and metabolic sub-routines.

  • Produce toxic hydrogen peroxide ($H_2O_2$) as a metabolic byproduct, which is immediately rendered harmless into water and oxygen by the enzyme catalase.

  • Vacuoles:

  • Membrane-bound storage compartments prominent in plants, fungi, and protists. The plant central vacuole maintains cellular tonicity, regulates water/solute volume, and provides structural turgor.

• Mitochondria: Structural Features and Oxidative Metabolism

  • Present in virtually all eukaryotic cells as primary cellular generators of ATP via oxidative metabolism.

  • Double-Membrane Architecture:

  • Outer Membrane: Smooth and permeable to small solutes.

  • Intermembrane Space: Compartment situated between outer and inner membranes.

  • Inner Membrane: Extensively folded into internal shelves termed cristae, increasing surface area for embedded electron transport chain proteins and ATP synthase enzymes.

  • Mitochondrial Matrix: The fluid space enclosed within the inner membrane containing enzymes that catalyze the Krebs cycle, releasing carbon dioxide ($CO_2$) from pyruvic acid, fatty acids, and amino acids.

  • Autonomous Features: Possesses a self-replicating circular DNA genome and prokaryotic-like ribosomes.

• Chloroplasts: Structural Features and Photosynthetic Fixation

  • Photosynthetic organelles found in plants, algae, and photosynthetic protists that convert solar energy into chemical energy stored in carbohydrates.

  • Three-Membrane Architecture:

  • Outer Membrane: Encloses the organelle.

  • Inner Membrane: Surrounds the internal fluid-filled matrix called the stroma.

  • Thylakoid Membrane System: Internal network of flattened fluid-filled sacs called thylakoids stacked into column-like structures termed grana (singular: granum). The fluid interior of a thylakoid sac is the lumen.

  • Photosynthetic Pigments: Chlorophyll and carotenoid pigments embedded within thylakoid membranes capture light energy to produce ATP and NADPH, which are then used by metabolic enzymes in the stroma to fix atmospheric $CO_2$ into glucose.

  • Autonomous Features: Contains a circular DNA genome and ribosomes.

• Endosymbiotic Theory and Nitrogen-Fixing Organelles

  • Theory Definition: Proposes that mitochondria and chloroplasts originated as free-living prokaryotic cells (an ancestral aerobic proteobacterium and photosynthetic cyanobacterium, respectively) that were engulfed by ancestral eukaryotic host cells through endosymbiosis.

  • Supporting Evidence: Mitochondria and chloroplasts replicate independently via binary fission-like division, retain their own circular DNA genomes similar to bacterial chromosomes, and synthesize proteins using 70S prokaryotic-type ribosomes.

• Discovery of UCYN-A (Nitroplast): An international research team discovered that the marine nitrogen-fixing cyanobacterium candidate UCYN-A has transitioned from an endosymbiont to a permanent, fully integrated nitrogen-fixing organelle residing inside marine algal cells.

The Cytoskeleton, Extracellular Matrix, and Cellular Motility

• Overview of the Cytoskeleton

  • A dynamic network of protein filaments extending throughout the eukaryotic cytoplasm that supports cell structure, anchors organelles, enables intracellular transport, and generates cellular movement.

• The Three Cytoskeletal Filaments

  • Actin Filaments (Microfilaments):

  • Composed of two globular actin protein chains twisted into a helical strand ($7\,\text{nm}$ diameter).

  • Responsible for cellular movements including muscle contraction, cytoplasmic streaming, cell crawling, and pinching during cell division (cleavage furrow).

  • Microtubules:

  • The largest cytoskeletal element ($25\,\text{nm}$ diameter), forming hollow rigid tubes composed of $\alpha$-tubulin and $\beta$-tubulin heterodimers.

  • Continually assemble and disassemble; facilitate internal organelle positioning, chromosome segregation during mitosis, vesicular transport, and cell propulsion via cilia/flagella.

  • Intermediate Filaments:

  • Extremely stable, rope-like fibrous protein assemblies (diameter $8\text{--}10\,\text{nm}$) composed of diverse subunits (e.g., vimentin, keratin, neurofilaments).

  • Provide mechanical structural stability to tissues and anchor nucleus and organelles in fixed cytoplasm positions.

• Intracellular Motor Protein Transport

  • Four components are required to transport cargo along internal microtubule tracks:

  1. Cargo: The transport vesicle or organelle being moved.

  2. Motor Protein: Dynein (drives retrograde transport toward the minus-end) or Kinesin (drives anterograde transport toward the plus-end).

  3. Connector Complex: Adaptor proteins such as the Dynactin complex that link the motor protein to the cargo vesicle.

  4. Microtubule Track: The polarized tubulin polymer pathway along which the motor protein "walks" via ATP hydrolysis.

• Extracellular Matrix (ECM) Architecture and Functional Applications

  • Animal Cell ECM Structure: Lacking cell walls, animal cells secrete an extensive extracellular meshwork consisting of fibrous glycoproteins—primarily collagens, elastin, fibronectin, and glycosaminoglycans like Hyaluronic Acid (HA) attached to proteoglycans.

  • Integrin Transmembrane Linkage: Transmembrane adhesion proteins called integrins bind externally to ECM fibronectin and internally to intracellular actin microfilaments, mechanically coupling the external matrix directly to the internal cytoskeleton to transmit signaling cues and regulate cell behavior.

• Cosmetic and Clinical Applications:

  • Purified collagen and hyaluronic acid carbohydrates are directly injected as facial dermal fillers (e.g., Restylane, Juvéderm, Radiesse, Sculptra).

  • Tenascin-C (TnC): Research by Alessandra Sacco demonstrated that the ECM protein Tenascin-C is upregulated in muscle stem cells following tissue injury, reactivating regenerative repair pathways.

  • Mechanisms of Cell Motility

• Amoeboid Crawling: Actin microfilament polymerization rapidly pushes the cell's leading edge membrane outward, forming a pseudopodium. Integrins establish new adhesion focal points with the ECM substrate, while actin-myosin contraction at the cell rear detaches trailing focal points, pulling the cell body forward.

• Flagellar and Ciliary Swimming: Eukaryotic flagella and cilia consist of a membrane-enclosed bundle of microtubules arranged in a $9+2$ array (nine outer doublet microtubules encircling a central pair of single microtubules). Dynein motor arms anchored on adjacent doublets hydrolyze ATP to cause sliding forces that bend the structure. The arrangement is rooted in the cell by a basal body exhibiting a $9+0$ array of microtubule triplets.

Cell Identity, Cell-Cell Connections, and Intercellular Communication

• Cell-Surface Identity Recognition

  • Surface glycolipids dictate tissue-specific marker identity (e.g., A, B, O blood group carbohydrate antigens).

  • Major Histocompatibility Complex (MHC) Proteins: Transmembrane surface glycoproteins that present peptide fragments, permitting immune system cells to distinguish between "self" cellular markers and foreign "non-self" pathogens.

• Animal Cell Junctions

  • Tight Junctions: Impermeable junctional complexes formed by transmembrane proteins that tightly stitch adjacent plasma membranes together in epithelial sheets, creating a leak-proof barrier that prevents paracellular fluid diffusion.

  • Adhesive Junctions (Desmosomes & Hemidesmosomes): Mechanical junctional complexes that link the cytoskeletons of adjacent cells. Cadherin transmembrane proteins bind neighbor cadherins across the intercellular space and connect internally to dense cytoplasmic protein plaques anchored to intermediate filaments. Hemidesmosomes mechanically link intermediate filaments to the basal lamina ECM.

  • Communicating (Gap) Junctions: Intercellular channels formed by hexameric rings of transmembrane proteins called connexons. Two aligned connexons form an open cylindrical channel ($1.5\,\text{nm}$ internal diameter) connecting adjacent cytoplasms, permitting direct pass-through of water, inorganic ions, and small second messengers (e.g., enabling synchronized intracellular calcium $Ca^{2+}$ wave propagation across heart muscle tissue).

• Plant Cell Intercellular Junctions: Plasmodesmata

  • Specialized channels penetrating plant cell walls lined continuously with plasma membrane that physically connect the cytoplasm of adjacent plant cells.

  • Contain a central membrane tubule (desmotubule) connected directly to the smooth endoplasmic reticulum of both cells, enabling solute, nutrient, and signal passage.