Quantitative Fundamentals of Molecular and Cellular Bioengineering

by Wittrup, Tidor, Hackel, Sarkar

ISBN: 9780262042659 | Copyright 2019

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A comprehensive presentation of essential topics for biological engineers, focusing on the development and application of dynamic models of biomolecular and cellular phenomena.

This book describes the fundamental molecular and cellular events responsible for biological function, develops models to study biomolecular and cellular phenomena, and shows, with examples, how models are applied in the design and interpretation of experiments on biological systems. Integrating molecular cell biology with quantitative engineering analysis and design, it is the first textbook to offer a comprehensive presentation of these essential topics for chemical and biological engineering.

The book systematically develops the concepts necessary to understand and study complex biological phenomena, moving from the simplest elements at the smallest scale and progressively adding complexity at the cellular organizational level, focusing on experimental testing of mechanistic hypotheses. After introducing the motivations for formulation of mathematical rate process models in biology, the text goes on to cover such topics as noncovalent binding interactions; quantitative descriptions of the transient, steady state, and equilibrium interactions of proteins and their ligands; enzyme kinetics; gene expression and protein trafficking; network dynamics; quantitative descriptions of growth dynamics; coupled transport and reaction; and discrete stochastic processes. The textbook is intended for advanced undergraduate and graduate courses in chemical engineering and bioengineering, and has been developed by the authors for classes they teach at MIT and the University of Minnesota.

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Cover (pg. i)
Title (pg. iii)
Contents (pg. v)
Preface (pg. xiii)
Acknowledgments (pg. xv)
Ch 1 Introduction to Biological Rate Processes (pg. 1)
1.1 Biological Rate Processes (pg. 1)
1.2 Why Develop a Model? (pg. 9)
1.3 Mechanistic Model Formulation (pg. 10)
1.4 Model Validation (pg. 16)
1.5 Basic Themes in Rate Process Modeling (pg. 22)
Suggestions for Further Reading (pg. 27)
References (pg. 27)
Ch 2 Noncovalent Binding Interactions (pg. 29)
2.1 Kinetic Rate Constants (pg. 31)
2.2 Thermodynamics (pg. 34)
2.3 Energetic Contributions to Binding Affinity (pg. 43)
2.4 Energetics of Protein Binding Interfaces (pg. 51)
2.5 Environmental Impacts on Binding Rate (pg. 64)
2.6 Molecular Measurements: Light-Matter Interactions (pg. 75)
2.7 Fluorescence Applications for Biomolecular Measurements (pg. 89)
Suggestions for Further Reading (pg. 101)
Problems (pg. 102)
References (pg. 106)
Ch 3 Binding Equilibria and Kinetics (pg. 111)
3.1 Equilibrium Monovalent Protein-Ligand Binding (pg. 111)
3.2 Binding Kinetics (pg. 115)
3.3 Multiple Binding Sites (pg. 121)
3.4 Fast or Complex Reaction Measurements (pg. 149)
3.5 Theory and Practice of Biomolecular Measurements (pg. 152)
3.6 General Issues in Measuring Binding Affinity and Kinetics (pg. 153)
3.7 Methods That Detect Altered Localization on Binding (pg. 159)
3.8 Methods to Detect Changes in Intrinsic Properties on Binding (pg. 174)
3.9 Fitting Models to Data (pg. 179)
Suggestions for Further Reading (pg. 190)
Problems (pg. 191)
References (pg. 206)
Ch 4 Enzyme Kinetics (pg. 209)
4.1 Enzymes Are Catalysts (pg. 209)
4.2 Enzymatic Rate Laws (pg. 212)
4.3 Reversible Enzyme Inhibition (pg. 235)
4.4 Signaling Pathways (pg. 251)
4.5 Metabolism (pg. 257)
4.6 Hydrolytic Regulatory Enzymes (pg. 260)
Suggestions for Further Reading (pg. 270)
Problems (pg. 270)
References (pg. 277)
Ch 5 Gene Expression and Protein Trafficking (pg. 281)
5.1 Synthesis, Degradation, and Growth (pg. 281)
5.2 Compartmental Models of Protein Sorting (pg. 297)
Suggestions for Further Reading (pg. 317)
Problems (pg. 317)
References (pg. 320)
Ch 6 Network Dynamics (pg. 323)
6.1 Nonlinear Dynamics (pg. 324)
6.2 Switches and Thresholds (pg. 337)
6.3 Adaptation (pg. 351)
6.4 Oscillations (pg. 359)
Suggestions for Further Reading (pg. 367)
Problems (pg. 368)
References (pg. 370)
CH 7 Population Growth and Death Models (pg. 373)
7.1 Typical Growth Curves (pg. 374)
7.2 Limitations on Growth of Cell Cultures (pg. 389)
7.3 Bioreactors (pg. 396)
7.4 Cell and Organismal Death (pg. 413)
7.5 Compartmental Growth Models (pg. 431)
Suggestions for Further Reading (pg. 461)
Problems (pg. 462)
References (pg. 471)
Ch 8 Coupled Transport and Reaction (pg. 477)
8.1 Diffusion, Collision, and Binding (pg. 477)
8.2 Scaling Analyses of Tissue Penetration (pg. 500)
8.3 Compartmental Models (pg. 504)
8.4 Macromolecular Crowding (pg. 512)
Suggestions for Further Reading (pg. 520)
Problems (pg. 520)
References (pg. 525)
CH 9 Discrete Stochastic Processes (pg. 527)
9.1 Poisson Statistics (pg. 528)
9.2 Stochastic Simulations (pg. 535)
9.3 Stochastic Gene Expression (pg. 551)
9.4 Stochasticity in Phage Infection (pg. 552)
9.5 Diffusion and Random Walks (pg. 554)
9.6 Combinatorial Bioinformatics (pg. 556)
Suggestions for Further Reading (pg. 564)
Problems (pg. 564)
References (pg. 567)
Index (pg. 569)

K. Dane Wittrup

K. Dane Wittrup is C. P. Dubbs Professor of Chemical Engineering and Biological Engineering at MIT and the Koch Institute for Integrative Cancer Research at MIT.

Bruce Tidor

Bruce Tidor is Professor of Biological Engineering and Computer Science at MIT.

Benjamin J. Hackel

Benjamin J. Hackel is Associate Professor of Chemical Engineering and Materials Science at the University of Minnesota.

Casim A. Sarkar

Casim A. Sarkar is Associate Professor of Biomedical Engineering at the University of Minnesota.

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