Principles and Models of Biological Transport 2nd Edition

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 PREFACE TO THE SECOND EDITION

Focus, Organization, and Content

This book, like the first edition, deals with the mass transport processes that take place
in living systems, with a focus on the normal behavior of eukaryotic cells and the or-
ganisms they constitute, in their normal physiological environment. As a consequence
of this focus, the structure and content of the book differ from those of traditional
transport texts. We do not start with the engineering principles of mass transport
(which are well presented elsewhere) and then seek biological applications of these
principles; rather, we begin with the biological processes themselves, and then de-
velop the models and analytical tools that are needed to describe them.
This approach has several consequences. First of all, it drives the content of the
text in a direction distinctively different from conventional transport texts. This is be-
cause the tools and models needed to describe complex biological processes are often
different from those employed to describe more well-characterized inanimate systems.
Many biological processes must still be described phenomenologically, using meth-
odologies like nonequilibrium thermodynamics. Simple electrical analogs employing
a paucity of parameters can be more useful for characterization and prediction than
complex theories based on the behavior of more well-defined systems on a laboratory
bench. By allowing the biology to drive the choice of analysis tools and models, the
latter are consistently presented in the context of real biological systems, and analysis
and biology are interwoven throughout.
Owing to its more biological focus, the book includes more biology and physiol-
ogy than most texts on engineering in the life sciences, and some parts will be easier
to follow for readers with some background in biology. To keep the text self-
contained in this respect, an early chapter is devoted to those aspects of cell biology
most relevant to biological transport systems.
A few words on the use of the term “models” in the title. The explosive growth of
molecular biology in the past several decades demands that space be devoted to the
molecular-level events that underlie the observables of biological transport. This
means that “models” must now be understood to include physical and structural mod-
els of transport systems and processes at the molecular level, as well as the mathe-
matical models of transport that continue to be developed to describe biological trans-
port mechanisms at all levels.
The text includes chapters that deal primarily with fundamental transport princi-
ples, including thermodynamics (Chapters 1, 2, 6); the cell, including intracellular
transport (Chapter 3); the biological transport mechanisms, such as channels and car-
riers, employed by living organisms (Chapters 4, 5, 7), and applications of these
mechanisms in control and in the function of tissues and organs such as kidney and
vii
viii PREFACE

lung (Chapters 8–11). A more thorough overview of the text can be gained by review-
ing the detailed Table of Contents that follows. The models in latter chapters are de-
rived using the principles presented in earlier ones, so the student appreciates the as-
sumptions that underlie them, and their consequent limitations. Those aspects of
transport that are closely associated with specific tissues — for instance, the Hodgkin-
Huxley theory of axonal conduction — are presented in these latter chapters.
Certain topics are dealt with less thoroughly in this text, or are outside its scope.
Experimental techniques used in transport research are well described in the extensive
methods literature and are not discussed here in great detail. Experimental data are
presented primarily to illustrate specific transport mechanisms, so the selection of data
is representative rather than complete. Transport phenomena that exist only in ex-
perimental settings — for instance, isotope interaction effects — are not discussed. On
the other hand, the text will provide guidance to the experimenter regarding the ap-
propriate tools to interpret experimental data, and the limits on their applicability.
The emphasis of the text is on mass transfer. Both convection and diffusion are
included, but purely convective transport, such as the transport of oxygen in large
blood vessels or gas flow in the early generations of the respiratory tree, is not. The
transfer of momentum, i.e., fluid mechanics, is not dealt with in any depth. Fortu-
nately, there are several recent texts on biological fluid mechanics, particularly in the
cardiovascular area. Heat transfer is also outside the scope.
Some final comments on style:
— the system of units used in the text is centimeter-gram-second (cgs)
rather than Système International (SI), since the former units still
dominate the literature. Conversions between the two systems are
presented in Chapter 1.
— the valences of ions are not shown in the text; sodium ion is desig-
+
nated by Na, not Na . The reader is assumed to know that metals and
halogens are ionized in the biological milieu.

Use in the Classroom

The text is designed for a first course in biological mass transport and is based on
courses I have taught to students primarily, but not exclusively, in biomedical engi-
neering at Johns Hopkins, Ohio State, and Duke. As is appropriate for an engineering
course, the student is assumed to have a certain facility with modeling and mathemat-
ics. The material is presented at a level easily accessible to upper-class undergraduates
or early graduate students. The combination of biological content and engineering ap-
proach should be attractive not only to biomedical engineering students, but also to
students in chemical, mechanical, and environmental engineering who are interested
in the life sciences. The text can also be used to provide a broader perspective for stu-
dents in physiology and biophysics, or with students in the biological sciences who
are interested in a more quantitative approach to transport.
Though mathematical modeling is an essential component of the text, the equa-
tions are not exceptionally complex, for several reasons. Most biological transport
PREFACE ix

processes can be described by steady-state equations, and even transients are generally
quasisteady with respect to mass transfer. Most membrane transport models assume
no variation in the variables of interest in the plane of the barrier. As a consequence,
with rare exceptions (most notably Chapter 11 and to a lesser extent Chapter 9), the
mathematics is limited to ordinary differential equations.
On the life science side, an introductory knowledge of biology and chemistry is
assumed, a requisite which my current students meet with a first college course in bi-
ology. A third discipline that supports the models developed in the text is thermody-
namics, a subject not always included in the crowded curriculum. Accordingly, sepa-
rate chapters are devoted to equilibrium thermodynamics in solution and nonequi-
librium thermodynamics, prior to the treatment of diffusional and coupled transport,
respectively.
In addition to supporting a core or elective biological transport course, this text
could also provide a framework for teaching biology and physiology per se, as well as
biological modeling, to students in biomedical, chemical, and mechanical engineering.
Transport is relevant to most biological systems and, in contrast to many other subdis-
ciplines within biology, lends itself well to mathematical modeling and engineering
analysis. The book includes examples that relate to the cardiovascular system, nerve
transmission, kidney function, control systems, secretory activity, and other biological
systems and functions. It should be possible to design an undergraduate course in en-
gineering physiology that covers much of the subject in the context of biological
transport, perhaps supplemented with a module on cardiovascular fluid mechanics that
could be based on any of several recent texts in this area.
To support the use of the text in class, exercises are included at the end of each
chapter. Some of the exercises are thought problems; some require the student to ap-
ply the presented material quantitatively, and others encourage the student to explore
beyond the boundaries of the book itself.
More exciting and, if it meets its objectives, more useful, a website for the book
has been set up on the server at the Pratt School of Engineering at Duke. The URL of
the site is

http://biotrans.pratt.duke.edu/

The site will be accessible to students, instructors, and other users and is intended to
create a “community of the book” that will enhance both teaching and learning. Using
the site, community members will be able to post additional exercises; suggest new
material for inclusion in courses based on the text, either in general terms or with a
link to a specific publication; and share course syllabi. It can also be used to post cor-
rections or amendments to the text itself.
Users will be encouraged to register on a listserv so that they can be alerted when
something new has been posted on the site. If there is interest, the site can support fo-
rums on issues of common concern among the users. The website is intended to com-
plement the text and be a continuing resource in this important field.
x PREFACE

In Appreciation
In a sense, this book has many authors besides myself. It reflects the research efforts
of numerous investigators in biology and transport science, and insights from the au-
thors of many former texts. Many of the figures are gifts from colleagues and their
publishers, who graciously permitted me to reproduce or adapt their illustrations. Most
of the exercises have been vetted by my students at Ohio State and Duke. I would like
to single out a few people who either suffered through the writing or without whom it
would never have been completed:
— the students in my laboratory, to whom I was not always as available as I
would have liked during the past few years, particularly Yun Liang, who
found and copied all the references that had escaped digitization, and Ji
Zhang, who computed and produced all the new numerical plots in this
edition;
— Tim Oliver, who managed the project and patiently translated my computer
files into the pages that follow; the folks at HFS Imaging, who transformed
my often ambiguous sketches into the precise figures that appear through-
out; and my wife, Ann, who obtained the permissions that allowed us to
reproduce the excellent artwork of earlier authors.

Durham 2008 Morton H. Friedman

 CONTENTS

Preface ..................................................................................................................... vii

1: Equilibrium Thermodynamics
Introduction .......................................................................................................................... 1
1.1. Chemical Potentials and Activities .......................................................................... 1
1.1.1. Thermodynamic Preliminaries. The Electrochemical
Potential ...................................................................................................... 2
1.1.2. The Interphase Equilibrium Condition ....................................................... 4
1.1.3. Electrochemical Potentials in Terms of Measurable Solution
Variables: Introduction, and the Effect of Electrostatic Potential............... 5
1.1.4. The Gibbs–Duhem Equation ...................................................................... 5
1.1.5. Dependence of the Chemical Potential on Pressure.................................... 6
1.1.6. Dependence of the Chemical Potential on Composition............................. 7
1.1.7. Units ........................................................................................................... 11
1.1.8. Activity and Activity Coefficient ............................................................... 12
1.2. Ion Equilibrium across Membranes......................................................................... 14
1.2.1. The Nernst Equilibrium .............................................................................. 14
1.2.2. Origin of the Nernst Potential..................................................................... 15
1.2.3. Specific Ion Electrodes ............................................................................... 17
1.2.4. Activity Coefficient Considerations ........................................................... 17
1.2.5. The Donnan Equilibrium ............................................................................ 19
1.3. Chemical Equilibrium.............................................................................................. 21
Problems............................................................................................................................... 24

2: Free Diffusion
Introduction .......................................................................................................................... 29
2.1. Free Diffusion of Nonelectrolytes ........................................................................... 30
2.1.1. The Teorell Equation .................................................................................. 30
2.1.2. Integration of the Teorell Equation; Fick's First Law;
Solute Permeability..................................................................................... 31
2.1.3. Unstirred Layers ......................................................................................... 36
2.1.4. Applications of Solution Theory................................................................. 38
2.1.5. Fick's Second Law and Convective Diffusion ............................................ 40
2.1.6. Justification of the Steady-State Assumption:
Time Scales in Biological Transport........................................................... 41
2.2. Free Diffusion of Electrolytes ................................................................................. 43
2.2.1. Differences between Electrolyte and Nonelectrolyte Diffusion ................. 43
2.2.2. The Electrodiffusion Equation.................................................................... 44
2.2.3. Integration of the Electrodiffusion Equation .............................................. 47

xi
xii CONTENTS

2.2.4. Some Special Cases .................................................................................... 49

Equilibrium ......................................................................................... 49
Uniform Composition ......................................................................... 50
Diffusion Potential of a Bi-Ionic System............................................ 51
Active and Passive Exchange with a Closed Compartment................ 52
Equal Total Concentrations on the Two Sides of the
Membrane: The Constant-Field Equation....................................... 53
2.2.5. Ionic Permeability and the Resting Potential of the Cell ............................ 57
2.2.6. Charged Membranes................................................................................... 59
2.2.7. Limitations of the Electrodiffusion Equation and Its Solutions.................. 61
Problems............................................................................................................................... 62

3: The Cell
Introduction .......................................................................................................................... 67
3.1. Overview ................................................................................................................. 67
3.2. The Structure of an Animal Cell.............................................................................. 68
3.2.1. Composition and Structure of the Plasma Membrane................................. 68
Heterogeneity of Cell Membranes ...................................................... 68
The Mosaic Model of the Plasma Membrane ..................................... 72
The Glycocalyx and Surface Charge .................................................. 74
3.2.2. The Internal Structure of the Cell ............................................................... 75
3.3. Metabolism: The Production of ATP....................................................................... 78
3.4. Intracellular Transport ............................................................................................. 84
3.4.1. Intracellular Diffusion ................................................................................ 84
3.4.2. Protein Transport ........................................................................................ 87
Transport into the Nucleus.................................................................. 87
Transport into the Mitochondrion....................................................... 88
3.4.3. Vesicular Transport .................................................................................... 90
Endocytosis......................................................................................... 91
Exocytosis, Secretion and Transcytosis .............................................. 95
3.5. Cellular Motility and Locomotion ........................................................................... 100
3.5.1. Actin-Based Movement and Chemotaxis ................................................... 100
3.5.2. Cilia and Flagella........................................................................................ 105
Problems............................................................................................................................... 107

4: Facilitated Diffusion: Channels and Carriers

Introduction .......................................................................................................................... 111
4.1. Mechanisms of Channels and Carriers .................................................................... 112
4.1.1. Hallmarks of Mediated Transport............................................................... 112
4.1.2. Ion Selectivity of Channels......................................................................... 114
4.1.3. Energetics of Ion Selectivity, and Steric Effects......................................... 116
4.1.4. Ion Selectivity of Channels: Summary ....................................................... 119
4.1.5. The Structure of Ion Channels: Selectivity Filters,
Gates, and Energy Profiles.......................................................................... 120
CONTENTS XIII

4.1.6. Regulation of the Gating Process................................................................ 122

4.1.7. Classification of Ion Channels. Aquaporins and Gap Junctions ................. 131
4.1.8. Carrier Models ............................................................................................ 137
4.1.9. Carriers and Channels: Convergences and Differences .............................. 139
4.2. Kinetics of Facilitated Transport ............................................................................. 141
4.2.1. Models of Ion Channel Transport: Overview ............................................. 141
4.2.2. Energy Barrier and Binding Models of Channel Transport ........................ 143
Ionic Independence: Absolute Rate Theory........................................ 143
Saturable Channels: Kinetic Analysis................................................. 146
4.2.3. The Patch Clamp and Two Applications .................................................... 151
Acetylcholine Receptor Channel Kinetics .......................................... 152
Voltage and Current Sensitivity of a
Voltage-Activated Sodium Channel ............................................... 154
4.2.4. Stochastic Properties of Channels: Membrane Noise Analysis .................. 158
4.2.5. The Simplest Model of Carrier Transport: Assumptions............................ 161
4.2.6. The Simplest Model of Carrier Transport: Equations................................. 162
4.2.7. Monosaccharide Transport in the Erythrocyte............................................ 165
4.2.8. More Complex Carrier Models................................................................... 166
4.2.9. Exchangers and Cotransporters................................................................... 170
4.3. Inhibition of Facilitated Transport........................................................................... 174
4.3.1. Inhibition of Channel Transport: Channel Block........................................ 174
4.3.2. Inhibition of Carrier Transport ................................................................... 175
Problems............................................................................................................................... 179

5: Active Transport
Introduction .......................................................................................................................... 185
5.1. Active Transport: General Considerations .............................................................. 186
5.1.1. Metabolic Coupling and Affinity................................................................ 186
5.1.2. Classification of Active Transport Processes.............................................. 188
5.1.3. Identification of Active Transport Processes .............................................. 190
5.2. Mechanisms of Active Transport............................................................................. 190
5.2.1. Scalar Active Transport: Overview ............................................................ 191
5.2.2. Primary Scalar Transport ............................................................................ 192
5.2.3. Secondary Scalar Transport ........................................................................ 193
Cotransport ......................................................................................... 195
Countertransport ................................................................................. 197
5.2.4. Vectorial Active Transport, the Curie Theorem and
Substrate Activation.................................................................................... 199
5.2.5. Sodium–Potassium Exchange..................................................................... 202
5.2.6. Pump Selectivity and Other Properties Shared with Passive Carriers ........ 204
5.3. Kinetics of Active Transport ................................................................................... 205
5.3.1. A Simple Secondary Scalar Transport Model: Assumptions...................... 206
5.3.2. A Simple Secondary Scalar Transport Model: Equations........................... 208
5.3.3. More Complex Symport Models; the Sodium/Glucose Transporter........... 209
5.3.4. Primary Scalar Transport ............................................................................ 213
5.3.5. Flux Equations for Primary Scalar Transport ............................................. 214
xiv CONTENTS

5.3.6. Relation between the Coupling Parameter * and

the Affinity of the Metabolic Reaction ....................................................... 215
5.3.7. Vectorial Active Transport and the Nature of Na–K Exchange.................. 216
5.3.8. Pumps and Leaks ........................................................................................ 216
Problems............................................................................................................................... 220

6: Nonequilibrium Thermodynamics
Introduction .......................................................................................................................... 225
6.1. The Basic Phenomenological Equations.................................................................. 225
6.1.1. Conjugate Forces and Fluxes...................................................................... 225
6.1.2. Phenomenological Coefficients and Linear Thermodynamics ................... 227
6.1.3. Frictional Interpretation of the Phenomenological Equations..................... 229
6.1.4. A Cautionary Note before Proceeding........................................................ 230
6.2. Nonequilibrium Thermodynamic Description of Passive Transport ....................... 231
6.2.1. Setting the Stage ......................................................................................... 231
6.2.2. The Chemical Potential of the Solvent ....................................................... 232
6.2.3. A New Set of Forces and Fluxes; Osmotic Pressure................................... 234
6.2.4. The Kedem–Katchalsky Equations............................................................. 235
6.2.5. Physical Significance of the Reflection Coefficient:
Semipermeable Membranes and the Osmometer,
Steric Effects and Sieving........................................................................... 237
6.2.6. Osmotic Pressure of Solutions; Donnan Osmotic Pressure;
Osmotic Effects on Cells ............................................................................ 242
6.2.7. Passive Transport of Multiple Nonelectrolytes........................................... 246
6.2.8. Passive Transport of Electrolytes: Electrokinetic Phenomena.................... 247
6.3. Nonequilibrium Thermodynamic Description of Active Transport......................... 248
6.3.1. Definition of Active Transport ................................................................... 248
6.3.2. Coupling between Nonconjugate Forces and Fluxes .................................. 250
6.3.3. Nonequilibrium Thermodynamics of Motor Proteins
and ATP Synthase....................................................................................... 252
6.4. Limitations of Nonequilibrium Thermodynamics ................................................... 254
6.4.1. Closeness to Equilibrium: A Limitation Intrinsic to
Linearized Nonequilibrium Thermodynamics ............................................ 254
6.4.2. The Concentration Dependence of the Phenomenological
Coefficients................................................................................................. 257
6.4.3. Closeness to Equilibrium in Biological Systems ........................................ 258
6.4.4. The Information Content of Nonequilibrium Thermodynamics ................. 259
6.4.5. Approximations in the Derivation of the Kedem–Katchalsky
Equations .................................................................................................... 260
Problems............................................................................................................................... 261

7: Models of Transport across Cell Membranes

Introduction .......................................................................................................................... 265
7.1. Transport across the Lipid Bilayer of Cell Membranes........................................... 265
7.1.1. Evidence for Nonelectrolyte Diffusion across the Lipid Bilayer................ 266
7.1.2. A Simple Model of Transbilayer Diffusion ................................................ 267
CONTENTS XV

7.1.3. Potential Barriers in the Bilayer.................................................................. 269

7.2. Models of Transport through Pores ......................................................................... 270
7.2.1. Classification of Pore Transport Models .................................................... 271
7.2.2. Hydraulic Conductivity of a Pore ............................................................... 272
7.2.3. Hindered Diffusion; Solute Permeability as a Probe of Pore Radius.......... 273
7.2.4. Other Factors Affecting Estimated Pore Size; The Equivalent Pore........... 276
7.2.5. Hindered Convection (Sieving); the Reflection Coefficient as a
Probe of Pore Radius .................................................................................. 279
7.2.6. Combined Diffusion and Convection through Pores .................................. 282
7.2.7. Single-File Transport through Pores........................................................... 283
7.2.8. The Permeability Ratio of Larger Pores ..................................................... 287
7.3. Electrical Analogs.................................................................................................... 289
7.3.1. Equivalent Circuit for the Passive Flux of a Single Ion.............................. 289
7.3.2. Equivalent Circuit for the Passive Transport of Multiple Ions ................... 290
7.3.3. The Electrical Analog of a Rheogenic Pump.............................................. 293
7.3.4. Some Final Remarks................................................................................... 294
Problems............................................................................................................................... 295

8: Regulation and Feedback

Introduction .......................................................................................................................... 299
8.1. Regulation of Transport ........................................................................................... 301
8.1.1. Receptor-Mediated Second Messenger Systems: Cyclic
AMP and Antidiuretic Hormone................................................................. 301
8.1.2. Direct Hormonal Regulation without an Extracellular
Receptor: Aldosterone ................................................................................ 306
8.1.3. Calcium-Based Regulation ......................................................................... 307
Maintenance of a Low Cytosolic Calcium Concentration .................. 307
Calcium Signaling .............................................................................. 307
Calcium Handling in Cells and Compartmental Analysis .................. 309
8.2. Feedback in Transport Systems: Insulin.................................................................. 315
8.3. Regulation by Transport .......................................................................................... 317
8.3.1. Regulation of Cell Volume ......................................................................... 317
8.3.2. Regulation of Cell pH................................................................................. 322
Problems............................................................................................................................... 325
Appendix 8.1. Nonequilibrium Binding in Compartmental Analysis ................................ 327

9: Excitable Cells
Introduction .......................................................................................................................... 329
9.1. Nerve ....................................................................................................................... 330
9.1.1. The Resting Neuron.................................................................................... 331
9.1.2. The Action Potential: Electrical Aspects .................................................... 333
The Membrane Action Potential: Resting State.................................. 335
Hodgkin and Huxley's Equations for the Dependence
of Conductance on Membrane Potential ......................................... 337
Excitation of the Membrane Action Potential..................................... 340
xvi CONTENTS

The Propagating Action Potential: Cable Theory ............................... 343

The Role of Myelin............................................................................. 347
9.1.3. The Action Potential: Molecular Aspects ................................................... 349
Hodgkin and Huxley's Channel Model ............................................... 349
More Recent Models of the Potassium and
Sodium Channels of Nerve ............................................................. 353
9.1.4. Synaptic Transmission................................................................................ 359
9.2. Muscle ..................................................................................................................... 367
9.2.1. The Resting Muscle Fiber........................................................................... 368
9.2.2. Excitation and Excitation–Contraction Coupling ....................................... 370
Neuromuscular Transmission and Excitation:
The Acetylcholine Receptor ........................................................... 370
Excitation–Contraction Coupling ....................................................... 378
9.2.3. Molecular Mechanisms of Muscle Contraction .......................................... 382
Problems............................................................................................................................... 387

10: Epithelial Transport

Introduction .......................................................................................................................... 391
10.1. Organization of Epithelial and Endothelial Cell Layers and
Some Consequences ................................................................................................ 392
10.1.1. The Organization of Epithelial and Endothelial Cell Layers ...................... 392
10.1.2. The Pathways across Leaky and Tight Epithelia ........................................ 395
10.1.3. Transport in a Parallel Path System ............................................................ 400
10.1.4. Coupling of Transepithelial Water Flow to Active Ion Transport .............. 405
The Curran Model............................................................................... 405
The Standing Gradient Model............................................................. 407
The Sodium Recirculation Model....................................................... 410
The Cotransporter Hypothesis ............................................................ 411
10.1.5. The Effect of Unstirred Layers on Transepithelial Diffusion
and Osmosis: Concentration Polarization ................................................... 412
10.1.6. Electrical Analogs of Cell Layers ............................................................... 414
10.2. Examples of Epithelial and Endothelial Function ................................................... 418
10.2.1. Absorption .................................................................................................. 419
Absorption of Sugars in the Small Intestine ........................................ 419
Transport of Water and Sodium in the Proximal
Tubule of the Kidney ...................................................................... 422
Transport of Water and Sodium in the Distal Tubule
of the Kidney .................................................................................. 427
10.2.2. Secretion ..................................................................................................... 430
10.2.3. Filtration ..................................................................................................... 434
Problems............................................................................................................................... 439
Appendix 10.1. Convection, Diffusion and Mass Addition in Channel Geometries ........... 443

11: Gas Transport

Introduction .......................................................................................................................... 447
11.1. Partial Pressure and the Equations for Gas Flux...................................................... 448
CONTENTS XVII

11.2. Overview of the Gas Transport Process .................................................................. 449

11.3. Gas Exchange in the Lung....................................................................................... 453
11.4. Oxygen Transport in the Blood ............................................................................... 455
11.5. Transport from Red Blood Cells to Tissue .............................................................. 456
11.5.1. Reaction–Diffusion Processes .................................................................... 459
11.5.2. The Krogh Tissue Cylinder......................................................................... 461
11.5.3. Modifications to the Basic Krogh Model.................................................... 462
11.5.4. Beyond the Krogh Cylinder........................................................................ 468
Problems............................................................................................................................... 480

References ............................................................................................................... 485

Index ........................................................................................................................ 497

 1
EQUILIBRIUM THERMODYNAMICS

INTRODUCTION
It is appropriate to begin this text with an examination of the equilibrium state, since
departures from this state drive the transport processes that we will discuss in the
chapters to follow. The equilibrium state is defined in the first section of this chapter,
using the laws of thermodynamics to develop expressions for the activities and chemi-
cal potentials of species in the biological milieu. Because of the particular importance
of the chemical potential (and the related electrochemical potential) to descriptions of
transport, special emphasis is placed on its relation to solute activities and concentra-
tions, and to the other measurable properties of biological solutions.
Because of the close relation between equilibrium and transport, it is not surpris-
ing that a number of equilibrium thermodynamic concepts have become an integral
part of the description of certain transport processes. Two of these concepts are devel-
oped in this chapter for later use: ionic equilibria across membranes and at interfaces,
and chemical equilibrium and equilibrium constants.

1.1. CHEMICAL POTENTIALS AND ACTIVITIES

Among the several equivalent thermodynamic definitions of equilibrium, the one that
is based on chemical potential is particularly well suited to the purposes of this text.
This is because gradients or differences in chemical potential are the natural driving
forces for the fluxes of solute and solvent; they also drive the biochemical processes
to which these fluxes may be coupled. By using the chemical potential to define ther-
modynamic equilibrium, we achieve a certain ease of movement between equilibrium
considerations and transport events.
In the first part of this section, the condition for thermodynamic equilibrium be-
tween two phases is developed in terms of the chemical and electrochemical potentials
of the species in each phase. In biological transport, these phases are almost always
solutions, and the bulk of the section is devoted to the development of expressions for
the chemical and electrochemical potentials in terms of solution composition, pres-

M.H. Friedman, Principles and Models of Biological Transport, 1

DOI: 10.1007/978-0-387-79240-8_1, © Springer Science+Business Media, LLC 2008
2 CH. 1: EQUILIBRIUM THERMODYNAMICS

sure, and temperature. The section concludes with a brief discussion of solute activity
and concentration as they relate to the chemical potential.
A limited familiarity with thermodynamics is assumed. Accordingly, a few com-
mon thermodynamic terms are used here without definition, and the thermodynamic
development includes a small number of equations that are presented without proof
and whose derivation can be found in any thermodynamics text. These equations are
indicated with an asterisk.

1.1.1. Thermodynamic Preliminaries: The Electrochemical Potential

We begin with the First Law of Thermodynamics, in differential form:
*dU = dQ – dW. (1.1)
Here, dU is the change in the internal energy of a system of interest, dQ is a differen-
tial quantity of heat transferred into the system, and dW is a differential amount of
work performed by the system. The internal energy of the system is increased when
heat is added, and decreases when the system performs work.
Different systems can perform different kinds of work, including:
1. the movement of volume, or expansion, against an external pressure;
2. the movement of charge, for instance that on an ion, against an electro-
static potential; and
3. the transfer of material.
Corresponding to these,
*dW  PdV  \dq  œ Pi dni , (1.2)
i

where the sum includes all species in the system, P is hydrostatic pressure, V is the
volume of the system, \ is electrostatic potential, q is electric charge, Pi is the chemi-
cal potential of the ith species, and ni is the number of moles of the ith species in the
system. Equation (1.2) gives the differential work required to change, by differential
amounts, the volume, charge, and composition of the system.
We should note that there are other forms of work that systems can do, which we
will not include here. Among those having biological relevance, an important work
term appropriate to muscle is the work of shortening against a tensile force, F. If l is
the length of the muscle segment, the differential work of contraction is –Fdl.
The reversible addition or withdrawal of heat changes the entropy of the system,
according to the Second Law of Thermodynamics:
dQ
*dS  (1.3)
T
where S is entropy and T is absolute temperature. By substituting Eqs. (1.2) and (1.3)
into (1.1), the Gibbs equation is obtained:
PRINCIPLES AND MODELS OF BIOLOGICAL TRANSPORT 3

dU  TdS  PdV \dq œ Pi dni . (1.4)

i

The Gibbs free energy of the system is defined by:

G = U + PV – TS. (1.5)
The total differential of G is:
dG = dU + PdV + VdP – TdS – SdT. (1.6)
Substituting Eq. (1.4) into (1.6),
dG  \dq œ Pi dni VdP  SdT . (1.7)
i

Equation (1.7) specifies the change in the Gibbs free energy of a system resulting
from reversible changes in its charge, content, pressure and temperature. We shall see
shortly that this expression is crucial for defining the conditions under which a system
is in a state of equilibrium.
In this text, the most common source of charges in solution is ionic solutes. The
total charge qi carried by the ith ionic species is proportional to ni, and the first two
terms on the right-hand side of Eq. (1.7) can be combined. The coulombs of charge
carried by a mol or gram atom of the ith ion is:
qi = zi  ni, (1.8)
where zi is the valence of the ith ion and  is the Faraday, a conversion factor equal to
about 96,500 coul/mol.
The total charge in the system, q, is obtained by summing qi over i; its differential
is
dq  œ zi  dni. (1.9)
i

Substituting Eq. (1.9) into (1.7),

dG  \ œ z i dni œ Pi dni VdP  SdT . (1.10)
i i

Note that, although both sums are over all species, only charged species (zi z 0) con-
tribute to the first sum.
Define the electrochemical potential of the ith species by
P i  Pi zi\ . (1.11)

The electrochemical potential becomes identical to the chemical potential if the spe-
cies is uncharged. Equation (1.10) can now be written as
dG  œ P i dni VdP  SdT . (1.12)
i