Cell Membranes, Transport, Levels of Organization and Feedback Loops

1Overview

Every person began as one cell, and about every tissue in the body still depends on what that cell's descendants do at their outer boundary. The membrane that wraps a cell decides what enters, what leaves and what the cell can sense of its surroundings. Zoom out from the membrane and cells assemble into tissues, organs and organ systems; zoom out further and the whole organism must keep its internal conditions steady while the outside world keeps changing. This lesson follows that journey: the membrane and its transport mechanisms, the levels of organization from molecules to organism, and the feedback loops that regulate the body's internal environment.

2The cell membrane: a fluid, selective boundary

Every cell is enclosed by a plasma membrane, a double layer of phospholipids. As Lesson 1 described, each phospholipid has a hydrophilic head and two hydrophobic tails. In water the tails hide in the interior of the sheet and the heads face the watery fluid on each side, so the bilayer forms spontaneously. The membrane is fluid, not rigid: lipids and proteins drift sideways within it, which is why the structure is called the fluid mosaic model.

• Cholesterol is tucked among the phospholipids and helps regulate fluidity.
• Integral proteins span the membrane. Channel proteins let specific ions pass, carrier proteins bind and move particular molecules, and receptors bind signals such as hormones and neurotransmitters.
• Peripheral proteins sit on a surface and often act as enzymes; digestive enzymes on intestinal cells are an example.
• Glycoproteins and glycolipids carry short carbohydrate chains that form the glycocalyx, a cell-identity tag used in immune recognition and in the rejection of transplanted organs.

The membrane is selectively permeable. Small nonpolar molecules such as O₂, CO₂, lipids and alcohol dissolve in the lipid core and cross directly. Large polar molecules, ions and glucose cannot slip through the hydrophobic interior and need protein help.

3Passive transport: no ATP required

Particles are in constant random motion, and the net result is that they spread from where they are crowded to where they are scarce. This is movement down a concentration gradient, and it costs the cell no energy.

• Simple diffusion: movement through the bilayer itself, as with O₂ entering and CO₂ leaving cells.
• Facilitated diffusion: movement down the gradient through a channel or carrier protein, as with glucose and Na⁺. The protein provides a route, not energy.
• Osmosis: the diffusion of water across a selectively permeable membrane. Water moves toward the side with the higher solute concentration.
• Filtration: fluid and small solutes pushed across a membrane by hydrostatic pressure from high to low pressure, as in capillaries and the kidney (Lessons 8 and 12).

Tonicity: osmosis and the living cell

The effect of a surrounding solution on cell volume is called its tonicity.

In real life. Intravenous fluids are made isotonic so that red blood cells are neither shrunk nor burst. Drinking seawater makes a person more dehydrated, because the hypertonic fluid draws water from the body's cells and the kidneys cannot produce urine saltier than seawater.

4Active transport and vesicular transport: ATP required

Cells often need to move substances against their gradient, for example concentrating K⁺ inside and Na⁺ outside. That requires energy and a protein pump.

• Primary active transport: the pump uses ATP directly. The sodium-potassium pump moves 3 Na⁺ out and 2 K⁺ in for each ATP; it maintains the electrical gradient of nerve cells and consumes most of a neuron's ATP.
• Secondary active transport: uses a gradient previously built by a pump. A symporter moves two substances in the same direction, for example the sodium-glucose symporter in the intestine and kidney. An antiporter moves them in opposite directions, for example the sodium-hydrogen antiporter that helps regulate cell pH.

Very large particles travel in membrane bubbles called vesicles.

• Endocytosis brings material in. Phagocytosis ("cell eating") engulfs large particles such as bacteria, as in white blood cells. Pinocytosis ("cell drinking") takes in fluid and dissolved substances. Receptor-mediated endocytosis is selective; iron bound to transferrin enters red blood cell precursors this way.
• Exocytosis exports material when a vesicle fuses with the membrane, as in release of digestive enzymes, hormones and neurotransmitters.

5Organelles: the cell's internal organization

Inside the membrane the cytoplasm contains specialized compartments, the organelles. They explain how a cell divides labour.

Cell structure follows function. Muscle cells and neurons contain many mitochondria because they use large amounts of ATP, while liver cells contain many peroxisomes because of their role in detoxification.

6Investigating membrane transport

The Curricular Competencies for this course emphasize designing and evaluating investigations, and membrane transport is a good subject for practice. A common model is a piece of dialysis tubing, which acts as a selectively permeable membrane, filled with a solution and placed in another solution. A student can ask, for example, how the concentration of sucrose outside a tubing bag affects the change in its mass.

1. Question and prediction. "If the surrounding solution is more concentrated than the solution in the bag, the bag will lose mass because water will leave by osmosis."
2. Variables. The independent variable is the outside concentration; the dependent variable is percent change in mass; controlled variables are the volume of fluid in the bag, the time, the temperature and the type of tubing.
3. Measurement. Use a balance in grams, blot each bag the same way before weighing and repeat each concentration several times.
4. Analysis. Graph percent change in mass against concentration. The point where the line crosses zero estimates the concentration that is isotonic to the bag's contents.
5. Evaluation. Discuss sources of error such as uneven blotting, leaks or tubing that is slightly permeable to the solute, and distinguish accuracy (closeness to the true value) from precision (agreement between repeated trials).

Membrane transport in the organ systems

The mechanisms above return in nearly every later lesson, which is why the membrane is more than a topic by itself.

7Micro to macro: levels of organization

Biological structure is hierarchical. Each level has properties that do not exist at the level below, a feature called emergent properties: no single heart cell pumps blood, but billions arranged correctly do.

1. Chemical (molecules). Atoms bond into molecules, the building blocks of every body structure (Lesson 1).
2. Organelles. Molecules assemble into functional compartments such as the nucleus and mitochondria.
3. Cellular. The cell is the smallest independently functioning unit of life.
4. Tissue. A group of similar cells working together on a specific function.
5. Organ. An anatomically distinct structure made of two or more tissue types.
6. Organ system. A group of organs that work together to carry out a major function.
7. Organism. A living being that can independently perform all life functions.

There are four primary tissue types. Epithelial tissue forms sheets that cover surfaces, line cavities and form glands (skin epidermis, the lining of the intestine). Connective tissue binds, supports and protects (fat, bone, tendons, blood). Muscle tissue is excitable and contracts: skeletal (voluntary), smooth (in the walls of internal organs) and cardiac (in the heart). Nervous tissue is excitable and carries electrochemical signals through the brain, spinal cord and nerves.

The body is divided into eleven organ systems: integumentary, skeletal, muscular, nervous, endocrine, cardiovascular, lymphatic, respiratory, digestive, urinary and reproductive. Lessons 6 to 13 examine the last eight. Organs often serve more than one system; the pancreas, for example, is part of both the digestive and endocrine systems, and the lung is a respiratory organ with an endocrine-like role in activating a blood-pressure hormone.

8Homeostasis and feedback loops

Cells work only within narrow limits of temperature, pH, glucose, water and ion concentration. Homeostasis is the maintenance of a relatively stable internal environment despite changes inside and outside the body. Each regulated variable has a set point (normal body temperature is about 37°C) and a normal range that fluctuates a little above and below it. The body holds these values by feedback loops.

Negative feedback

In negative feedback the response reverses the deviation. It is the most common mechanism and has three parts:

1. a sensor (receptor) monitors a value and reports it;
2. a control centre compares the value to the normal range and decides whether a response is needed;
3. an effector carries out a change that returns the value toward the set point.

Body temperature. When the body overheats, skin blood vessels dilate, sweat glands increase output and breathing deepens, so heat is lost. When the body cools, skin blood flow decreases and shivering begins, while thyroid hormone and epinephrine increase heat production.

Blood glucose. After a meal, pancreatic beta cells detect the rise and release insulin, which prompts muscle, fat and liver cells to take up glucose. As glucose falls, insulin release drops and alpha cells release glucagon so that glucose does not drop below normal (Lesson 7).

Blood CO₂ and breathing. A rise in blood CO₂ lowers pH; chemoreceptors report this to the brain stem, which increases breathing rate and depth, exhaling CO₂ and restoring pH (Lesson 10).

Positive feedback

In positive feedback the response amplifies the change and drives the variable further from where it began. It is normal only when it has a definite end point.

• Childbirth. Stretching of the cervix signals the brain to release oxytocin. Oxytocin strengthens contractions, which push the baby lower and stretch the cervix further, releasing more oxytocin. The loop ends when the baby is born and stretching stops.
• Blood clotting. Substances released at an injury start clotting, and each step stimulates more clotting, as platelets release ADP that recruits more platelets and the clotting cascade activates itself step by step. Tight control keeps the clot localized (Lesson 8).

In real life. A thermostat is a good analogy for negative feedback. A room heater is switched off when the sensor reads above the set temperature and on when it reads below. The body works the same way with more sensors and many effectors, and each of the later lessons examines the loops of one organ system.

Homeostasis is therefore an outcome of interactions among every level of organization: molecules (buffers and enzymes), cells (membrane transport), tissues and organs (sensors and effectors) and organ systems (nervous and endocrine control). When feedback fails, the result is disease, which Lesson 14 examines.

?Quick check

Try each question first, then reveal the answer.