LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the types of chemical bonds that hold atoms together in molecules.

• Understand the difference between polar and nonpolar molecules, and the important role that polarity plays in interactions of biological molecules.

• Understand the basic concepts of biochemical energetics, including the role of adenosine-5′-triphosphate (ATP) in the transformation of energy into biochemical work.

• Understand the concepts of acids, bases, pH, and buffering.

• Know the major classes of biological polymers: proteins, polysaccharides, and nucleic acids.

• Understand the chemical structure of polysaccharides as polymers of monosaccharides, including the simple sugars glucose, galactose, and fructose.

• Understand the basic structure of nucleic acids as polymers of nucleotides and how that structure is different in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) polymers.

• Understand the basic structure of proteins, which are polymers of amino acids, and how the diversity of amino acid structure influences protein three-dimensional structure and function.

• Understand how the chemical structure of phospholipids contributes to the properties of biological membranes.

• Understand the basic features of biological membranes, which are lipid bilayers that are decorated with proteins and carbohydrates.

• Understand the mechanisms of diffusion and osmotic pressure generation.

Prelude

Biomedical engineers are engaged in a great diversity of activities: Chapter 1 described many of the fields in which biomedical engineers make significant contributions. This chapter, together with Chapters 3 and 4, reviews fundamental chemistry concepts that are important for understanding human physiology and biomedical engineering (BME).

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the role of the excretory systems in eliminating wastes and toxins and maintaining body balances.

• Understand the concept of biotransformation and the role of the liver in accomplishing the removal of compounds by both direct excretion (through the biliary system) and biotransformation.

• Understand the basic anatomy of the kidney and its functional unit, the nephron.

• Understand the basic processes that underlie kidney function: filtration, reabsorption, and secretion.

• Understand the biophysical processes responsible for filtration and regulation of filtration in the glomerulus.

• Understand the concept of clearance and be able to calculate clearances for typical solutes.

• Understand how proteins in the membrane of tubular epithelial cells—such as channels, active transporters, co-transporters, and exchangers—are responsible for reabsorption and secretion of compounds.

• Understand the role of osmotic pressure as a driving force for water reabsorption in the tubules.

Prelude

Each person ingests a large number of molecules per day with meals and snacks (Figure 9.1). A similarly large number of molecules enters the body through respiration (Figure 9.2). Body processes—such as building proteins, producing energy, and replenishing lost nutritional stores—use many of these molecules (recall Table 7.1). But a sizeable number of ingested chemicals are either not usable or not needed by the body, and therefore must be eliminated. In addition, metabolic processes generate waste products that are toxic if they accumulate in body tissues. These molecules must also be eliminated.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the concept of affinity of a ligand for its associated receptor.

• Understand the principle of signal transduction, and how signals can be activated by ligand binding to a receptor.

• Understand the role of action potentials in signaling within the nervous system.

• Understand how protein and steroid hormones provide circulating signals in the endocrine system.

• Understand the diverse roles of signaling within the immune system.

Prelude

Chapter 5 provided background on the structure and function of human cells, which are the main functional units of the body. Most cells are fully independent living entities, capable of consuming nutrients, growing, and functioning autonomously. The human body is a collection of trillions of cells and, amazingly, these units act in a coordinated fashion, so that people can walk (usually without bumping into walls), breathe (without consciously motivating each breath), and kill invading pathogens (without knowing that they are there). How is the operation of all of these cells coordinated? This chapter reviews how cells communicate with each other directly and through signaling molecules to relay signals from outside and inside the cell (Figure 6.1).

Cells communicate with each other directly or indirectly via molecules called ligands. In direct cell–cell communication, the ligands are bound to the surface of the cell. Soluble, diffusible ligands are used for communication between cells that are not physically connected or are separated by long distances.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the importance of deoxyribonucleic acid (DNA) in storing genetic information in cells.

• Know the chemical structures of DNA and ribonucleic acid (RNA), and how these chemical structures are related to the functions of these biological macromolecules.

• Understand the mechanism of DNA replication and its importance in cell division.

• Understand the central dogma of molecular biology and the concepts of biological transcription and translation.

• Understand that RNA exists in different forms in the cell, with each form contributing uniquely to the processes of transcription and translation.

• Recognize the importance of gene cloning and how recombinant DNA technology has revolutionized biology and biomedical engineering (BME).

• Understand the technique of the polymerase chain reaction (PCR) and how it is used to synthesize DNA.

• Know the common gene delivery vectors that are used in human cells, as well as their advantages and disadvantages.

Prelude

One of the most fascinating and well-known stories in science is that of the discovery of the structure of DNA, which was accomplished by James Watson and Francis Crick in 1953, when both were young men working at Cavendish Laboratory in Cambridge, England. Watson's autobiographical book, The Double Helix, describes that period of accomplishment, but it retains its popularity because it deals directly with a more general theme. It might be the best description for modern readers of the magical quality of science and its appeal for young people seeking adventure, mystery, and fame.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the magnitude of the problem of cancer in modern society.

• Develop an elementary understanding of the biology of cancer cells and be able to describe some of the methods for characterizing the progression of tumors in cancer patients.

• Know some of the ways that ionizing radiation interacts with biological tissues and understand the use of radiation in treatment of solid tumors.

• Understand the role of surgery in diagnosis and treatment of tumors and be able to predict some of the ways that surgical treatments for cancer will develop in the future.

• Understand the value and limitations of chemotherapy in the treatment of cancer.

• Know about some of the new approaches, based on our understanding of the molecular and cellular biology of cancer, for creating biological treatments.

Prelude

Cancer is a common, often life-threatening, disease involving the uncontrolled growth and spread of abnormal cells. Cancer is one of the leading causes of death in the world, particularly in developed nations such as the United States. Cancer is really a group of diseases; it can arise in any organ of the body and has differing characteristics that depend on the site of the cancer, the degree of spread, and other factors. Mutations in certain genes within cells—called proto-oncogenes and tumor suppressor genes—are the primary cause of cancer (1).

Sadly, almost every college student has some knowledge of cancer, gained through experience with classmates, family members, or friends.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the role of vaccines in the prevention of disease.

• Understand the role of antibodies (Abs) in the immune system, and some of the ways that Abs can be used to prevent disease in humans.

• Understand the basic elements of Ab structure, and the difference in chemical structure between Ab classes.

• Understand the difference between monoclonal and polyclonal Abs.

• Understand how monoclonal antibodies (mAbs) are manufactured.

• Understand some of the basic approaches for vaccine development.

Prelude

The previous chapter introduced three of the major subjects of interest in biomolecular engineering: drug delivery, nanobiotechnology, and tissue engineering. This chapter focuses on additional applications of biomolecular engineering, particularly approaches for enhancing the function of the immune system. The most familiar application of biomedical engineering (BME) in immunology is the development of vaccines.

The development of vaccines that are both safe and effective has been one of the great achievements of modern medicine. Because of an effective vaccine, smallpox—a frequently fatal disease that claimed thousands of lives in previous centuries—has been eradicated, or eliminated as a natural infectious agent. Other severe infectious diseases, such as polio and influenza, are now in control in most countries of the world. There are, however, many diseases that have proven to be difficult for vaccine makers. Acquired immune deficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV), has killed millions of people worldwide (Figure 14.1), and there is still no effective vaccine available.

The field of biomedical engineering has expanded markedly in the past ten years. This growth is supported by advances in biological science, which have created new opportunities for development of tools for diagnosis of and therapy for human disease. This book is designed as a textbook for an introductory course in biomedical engineering. The text was written to be accessible for most entering college students. In short, the book presents some of the basic science knowledge used by biomedical engineers and illustrates the first steps in applying this knowledge to solve problems in human medicine.

Biomedical engineering now encompasses a range of fields of specialization including bioinstrumentation, bioimaging, biomechanics, biomaterials, and biomolecular engineering. Most undergraduate students majoring in biomedical engineering are faced with a decision, early in their program of study, regarding the field in which they would like to specialize. Each chosen specialty has a specific set of course requirements and is supplemented by wise selection of elective and supporting coursework. Also, many young students of biomedical engineering use independent research projects as a source of inspiration and preparation but have difficulty identifying research areas that are right for them. Therefore, a second goal of this book is to link knowledge of basic science and engineering to fields of specialization and current research.

As a general introduction to the field, this textbook assembles foundational resources from molecular and cellular biology and physiology and relates this science to various subspecialties of biomedical engineering.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the concepts of primary, secondary, tertiary, and quaternary structure in proteins.

• Understand the contribution of amino acid ionization to the structure of proteins.

• Understand the role of disulfide bonds in stabilizing protein structure.

• Recognize some of the methods used to determine the structure of proteins.

• Understand how post-translational modifications such as glycosylation and myristoylation contribute to protein structure and function.

• Understand the kinetics of enzyme action.

Prelude

Proteins are the workhorses of the cell (Figure 4.1): They provide structural support in the cytoskeleton, facilitate communication with other cells by acting as receptors, neutralize foreign pathogens, generate contraction forces in muscle, and most ubiquitously catalyze chemical reactions. Proteins are abundant in biological systems, such as eggs (Figure 4.2). Proteins are one of the major macronutrients in the human diet (Figure 4.3).

Some recombinant proteins now serve as therapeutic drugs for treatment or prevention of disease. Biomedical engineers also use recombinant proteins, such as growth factors, to promote growth and differentiation of cells in engineered tissues. Some biomedical engineers have been using techniques of protein engineering to design new biomaterials for use in tissue engineering, drug-delivery systems, or other medical applications.

This chapter describes the structure and function of proteins and also includes a brief introduction to some of the techniques used to determine protein structure, chiefly nuclear magnetic resonance (NMR) and x-ray crystallography. Researchers in the pharmaceutical industry use these protein structures in structure-guided drug design.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the concepts of an engineering system, system boundaries, and the differences between open and closed systems.

• Be familiar with the concepts of homeostasis and steady state and be able to distinguish equilibrium from steady state.

• Understand the concepts of external and internal respiration.

• Be familiar with air volumes and flow rates in the lungs.

• Understand how oxygen is carried by blood and the quantitative relationships describing oxygen concentration.

• Understand the relationship between carbon dioxide, bicarbonate ion, and pH in body fluids.

• Understand the diffusing capacity of the lung and how it relates to the properties of the respiratory membrane.

• Understand how the structure of the digestive organs (stomach, small intestine, large intestine, pancreas, and liver) is related to their functions in digestion.

• Understand the role of enzymes in digestion, and the importance of enzyme activation after secretion (i.e., the value of zymogens).

• Understand the role of reactor models in understanding digestion and absorption of nutrients.

Prelude

Humans eat, drink, and breathe to bring into their bodies the raw materials for growth, repair, and generation of the energy necessary for life and the actions that bring pleasure to life. This chapter provides an overview of human nutrition and respiration from the perspective of biomedical engineering (BME). The human body is an elegant machine that requires inputs for sustained operation. What are the processes responsible for input of nutrients and raw materials? How are molecular nutrients extracted from ingested materials? How are these processes controlled?

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand that the circulatory system consists of a circulating fluid, a system of vessels, and a pump.

• Know the composition of blood and the role of cells in determining blood's physical properties.

• Understand the general structure of the vascular system.

• Understand the relationship between vessel radius, resistance to flow, and pressure drop.

• Understand the function of capillaries in the distribution of flow throughout tissues and transport of molecules.

• Understand the anatomy of the heart and the electrical system that generates coordinated contractions.

• Understand the events in the cardiac cycle and how pressure is generated within the chambers and the aorta.

Prelude

Our bodies appear, from the outside, to be solid masses that are slow to change but, just beneath the surface, the body's fluids are in constant motion. Blood moves at high velocity throughout the body within an interconnected and highly branched network of vessels (Figure 8.1). The human circulatory system is responsible for the movement of fluid (and therefore vital nutrients contained in the fluid) throughout the body.

The purpose of the circulatory system is a familiar one to engineers and bakers; it provides mixing, and good mixing is an essential element of many successful enterprises. Cakes are made from flour, eggs, sugar, and milk (among other things); your birthday will be ruined (or at least a bit tarnished) if the chef does not mix these ingredients well. But why must humans be mixed?